Cell migration

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Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. [1] Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. [2] [3] An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells.

Contents

Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move. Cells achieve active movement by very different mechanisms. Many less complex prokaryotic organisms (and sperm cells) use flagella or cilia to propel themselves. Eukaryotic cell migration typically is far more complex and can consist of combinations of different migration mechanisms. It generally involves drastic changes in cell shape which are driven by the cytoskeleton. Two very distinct migration scenarios are crawling motion (most commonly studied) and blebbing motility. [4] [5] A paradigmatic example of crawling motion is the case of fish epidermal keratocytes, which have been extensively used in research and teaching. [6]

Cell migration studies

The migration of cultured cells attached to a surface or in 3D is commonly studied using microscopy. [7] [8] [5] As cell movement is very slow, a few μm/minute, time-lapse microscopy videos are recorded of the migrating cells to speed up the movement. Such videos (Figure 1) reveal that the leading cell front is very active, with a characteristic behavior of successive contractions and expansions. It is generally accepted that the leading front is the main motor that pulls the cell forward.

Common features

The processes underlying mammalian cell migration are believed to be consistent with those of (non-spermatozooic) locomotion. [9] Observations in common include:

The latter feature is most easily observed when aggregates of a surface molecule are cross-linked with a fluorescent antibody or when small beads become artificially bound to the front of the cell. [10]

Other eukaryotic cells are observed to migrate similarly. The amoeba Dictyostelium discoideum is useful to researchers because they consistently exhibit chemotaxis in response to cyclic AMP; they move more quickly than cultured mammalian cells; and they have a haploid genome that simplifies the process of connecting a particular gene product with its effect on cellular behaviour. [11]

Two different models for how cells move. A) Cytoskeletal model. B) Membrane Flow Model Cellmigrationmodels.png
Two different models for how cells move. A) Cytoskeletal model. B) Membrane Flow Model
(A) Dynamic microtubules are necessary for tail retraction and are distributed at the rear end in a migrating cell. Green, highly dynamic microtubules; yellow, moderately dynamic microtubules and red, stable microtubules. (B) Stable microtubules act as struts and prevent tail retraction and thereby inhibit cell migration. Microtubule in Cell Migration.jpg
(A) Dynamic microtubules are necessary for tail retraction and are distributed at the rear end in a migrating cell. Green, highly dynamic microtubules; yellow, moderately dynamic microtubules and red, stable microtubules. (B) Stable microtubules act as struts and prevent tail retraction and thereby inhibit cell migration.

Molecular processes of migration

There are two main theories for how the cell advances its front edge: the cytoskeletal model and membrane flow model. It is possible that both underlying processes contribute to cell extension.

Cytoskeletal model (A)

Leading edge

Experimentation has shown that there is rapid actin polymerisation at the cell's front edge. [12] This observation has led to the hypothesis that formation of actin filaments "push" the leading edge forward and is the main motile force for advancing the cell's front edge. [13] [14] In addition, cytoskeletal elements are able to interact extensively and intimately with a cell's plasma membrane. [15]

Trailing edge

Other cytoskeletal components (like microtubules) have important functions in cell migration. It has been found that microtubules act as "struts" that counteract the contractile forces that are needed for trailing edge retraction during cell movement. When microtubules in the trailing edge of cell are dynamic, they are able to remodel to allow retraction. When dynamics are suppressed, microtubules cannot remodel and, therefore, oppose the contractile forces. [16] The morphology of cells with suppressed microtubule dynamics indicate that cells can extend the front edge (polarized in the direction of movement), but have difficulty retracting their trailing edge. [17] On the other hand, high drug concentrations, or microtubule mutations that depolymerize the microtubules, can restore cell migration but there is a loss of directionality. It can be concluded that microtubules act both to restrain cell movement and to establish directionality.

Membrane flow model (B)

The leading edge at the front of a migrating cell is also the site at which membrane from internal membrane pools is returned to the cell surface at the end of the endocytic cycle. [18] [19] This suggests that extension of the leading edge occurs primarily by addition of membrane at the front of the cell. If so, the actin filaments that form there might stabilize the added membrane so that a structured extension, or lamella, is formed — rather than a bubble-like structure (or bleb) at its front. [20] For a cell to move, it is necessary to bring a fresh supply of "feet" (proteins called integrins, which attach a cell to the surface on which it is crawling) to the front. It is likely that these feet are endocytosed [21] toward the rear of the cell and brought to the cell's front by exocytosis, to be reused to form new attachments to the substrate.

In the case of Dictyostelium amoebae, three conditional temperature sensitive mutants which affect membrane recycling block cell migration at the restrictive (higher) temperature; [22] [23] [24] they provide additional support for the importance of the endocytic cycle in cell migration. Furthermore, these amoebae move quite quickly — about one cell length in ~5 mins. If they are regarded as cylindrical (which is roughly true whilst chemotaxing), this would require them to recycle the equivalent of one cell surface area each 5 mins, which is approximately what is measured. [25]

Rearward membrane flow (red arrows) and vesicle trafficking from back to front (blue arrows) drive adhesion-independent migration. Adhesion-independent migration.tif
Rearward membrane flow (red arrows) and vesicle trafficking from back to front (blue arrows) drive adhesion-independent migration.

Mechanistic basis of amoeboid migration

Adhesive crawling is not the only migration mode exhibited by eukaryotic cells. Importantly, several cell types — Dictyostelium amoebae, neutrophils, metastatic cancer cells and macrophages — have been found to be capable of adhesion-independent migration. Historically, the physicist E. M. Purcell theorized (in 1977) that under conditions of low Reynolds number fluid dynamics, which apply at the cellular scale, rearward surface flow could provide a mechanism for microscopic objects to swim forward. [27] After some decades, experimental support for this model of cell movement was provided when it was discovered (in 2010) that amoeboid cells and neutrophils are both able to chemotax towards a chemo-attractant source whilst suspended in an isodense medium. [28] It was subsequently shown, using optogenetics, that cells migrating in an amoeboid fashion without adhesions exhibit plasma membrane flow towards the cell rear that may propel cells by exerting tangential forces on the surrounding fluid. [26] [29] Polarized trafficking of membrane-containing vesicles from the rear to the front of the cell helps maintain cell size. [26] Rearward membrane flow was also observed in Dictyostelium discoideum cells. [30] These observations provide strong support for models of cell movement which depend on a rearward cell surface membrane flow (Model B, above). The migration of supracellular clusters has also been found to be supported by a similar mechanism of rearward surface flow. [31]

Schematic representation of the collective biomechanical and molecular mechanism of cell motion Collective Mechanism of Cell Motion.jpg
Schematic representation of the collective biomechanical and molecular mechanism of cell motion

Collective biomechanical and molecular mechanism of cell motion

Based on some mathematical models, recent studies hypothesize a novel biological model for collective biomechanical and molecular mechanism of cell motion. [32] It is proposed that microdomains weave the texture of cytoskeleton and their interactions mark the location for formation of new adhesion sites. According to this model, microdomain signaling dynamics organizes cytoskeleton and its interaction with substratum. As microdomains trigger and maintain active polymerization of actin filaments, their propagation and zigzagging motion on the membrane generate a highly interlinked network of curved or linear filaments oriented at a wide spectrum of angles to the cell boundary. It is also proposed that microdomain interaction marks the formation of new focal adhesion sites at the cell periphery. Myosin interaction with the actin network then generate membrane retraction/ruffling, retrograde flow, and contractile forces for forward motion. Finally, continuous application of stress on the old focal adhesion sites could result in the calcium-induced calpain activation, and consequently the detachment of focal adhesions which completes the cycle.

Polarity in migrating cells

Migrating cells have a polarity—a front and a back. Without it, they would move in all directions at once, i.e. spread. How this polarity is formulated at a molecular level inside a cell is unknown. In a cell that is meandering in a random way, the front can easily give way to become passive as some other region, or regions, of the cell form(s) a new front. In chemotaxing cells, the stability of the front appears enhanced as the cell advances toward a higher concentration of the stimulating chemical. From biophysical perspective, polarity was explained in terms of a gradient in inner membrane surface charge between front regions and rear edges of the cell. [33] This polarity is reflected at a molecular level by a restriction of certain molecules to particular regions of the inner cell surface. Thus, the phospholipid PIP3 and activated Ras, Rac, and CDC42 are found at the front of the cell, whereas Rho GTPase and PTEN are found toward the rear. [34] [35] [36] [37]

It is believed that filamentous actins and microtubules are important for establishing and maintaining a cell's polarity. [38] Drugs that destroy actin filaments have multiple and complex effects, reflecting the wide role that these filaments play in many cell processes. It may be that, as part of the locomotory process, membrane vesicles are transported along these filaments to the cell's front. In chemotaxing cells, the increased persistence of migration toward the target may result from an increased stability of the arrangement of the filamentous structures inside the cell and determine its polarity. In turn, these filamentous structures may be arranged inside the cell according to how molecules like PIP3 and PTEN are arranged on the inner cell membrane. And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell's outer surface.

Although microtubules have been known to influence cell migration for many years, the mechanism by which they do so has remained controversial. On a planar surface, microtubules are not needed for the movement, but they are required to provide directionality to cell movement and efficient protrusion of the leading edge. [17] [39] When present, microtubules retard cell movement when their dynamics are suppressed by drug treatment or by tubulin mutations. [17]

Inverse problems in the context of cell motility

An area of research called inverse problems in cell motility has been established. [40] [41] [32] This approach is based on the idea that behavioral or shape changes of a cell bear information about the underlying mechanisms that generate these changes. Reading cell motion, namely, understanding the underlying biophysical and mechanochemical processes, is of paramount importance. [42] The mathematical models developed in these works determine some physical features and material properties of the cells locally through analysis of live cell image sequences and uses this information to make further inferences about the molecular structures, dynamics, and processes within the cells, such as the actin network, microdomains, chemotaxis, adhesion, and retrograde flow.

See also

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Pseudopodia</span> False leg found on slime molds, archaea, protozoans, leukocytes and certain bacteria

A pseudopod or pseudopodium is a temporary arm-like projection of a eukaryotic cell membrane that is emerged in the direction of movement. Filled with cytoplasm, pseudopodia primarily consist of actin filaments and may also contain microtubules and intermediate filaments. Pseudopods are used for motility and ingestion. They are often found in amoebas.

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<span class="mw-page-title-main">Microfilament</span> Filament in the cytoplasm of eukaryotic cells

Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis, amoeboid movement, cell motility, changes in cell shape, endocytosis and exocytosis, cell contractility, and mechanical stability. Microfilaments are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility, one end of the actin filament elongates while the other end contracts, presumably by myosin II molecular motors. Additionally, they function as part of actomyosin-driven contractile molecular motors, wherein the thin filaments serve as tensile platforms for myosin's ATP-dependent pulling action in muscle contraction and pseudopod advancement. Microfilaments have a tough, flexible framework which helps the cell in movement.

Mechanotaxis refers to the directed movement of cell motility via mechanical cues. In response to fluidic shear stress, for example, cells have been shown to migrate in the direction of the fluid flow. Mechanotaxis is critical in many normal biological processes in animals, such as gastrulation, inflammation, and repair in response to a wound, as well as in mechanisms of diseases such as tumor metastasis.

<span class="mw-page-title-main">Podosome</span>

Podosomes are conical, actin-rich structures found as appendages on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 μm to 2.0 μm in diameter. While usually situated on the periphery of the cellular membrane, these unique structures display a polarized pattern of distribution in migrating cells, situating at the front border between the lamellipodium and lamellum. Their primary purpose is connected to cellular motility and invasion; therefore, they serve as both sites of attachment and degradation along the extracellular matrix. Many different specialized cells exhibit these dynamic structures such as invadopodia,, osteoclasts, vascular smooth muscle cells, endothelial cells, and certain immune cells such as macrophages and dendritic cells.

<span class="mw-page-title-main">Growth cone</span> Large actin extension of a developing neurite seeking its synaptic target

A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope. He first described the growth cone based on fixed cells as "a concentration of protoplasm of conical form, endowed with amoeboid movements". Growth cones are situated on the tips of neurites, either dendrites or axons, of the nerve cell. The sensory, motor, integrative, and adaptive functions of growing axons and dendrites are all contained within this specialized structure.

The lamellipodium is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate. Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia. The lamellipodium is born of actin nucleation in the plasma membrane of the cell and is the primary area of actin incorporation or microfilament formation of the cell.

<span class="mw-page-title-main">Filopodia</span> Actin projections on the leading edge of lamellipodia of migrating cells

Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as microspikes, and when they extend beyond the lamellipodia, they're known as filopodia. They contain microfilaments cross-linked into bundles by actin-bundling proteins, such as fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking them to the cell surface. Many types of migrating cells display filopodia, which are thought to be involved in both sensation of chemotropic cues, and resulting changes in directed locomotion.

<span class="mw-page-title-main">Cell cortex</span> Layer on the inner face of a cell membrane

The cell cortex, also known as the actin cortex, cortical cytoskeleton or actomyosin cortex, is a specialized layer of cytoplasmic proteins on the inner face of the cell membrane. It functions as a modulator of membrane behavior and cell surface properties. In most eukaryotic cells lacking a cell wall, the cortex is an actin-rich network consisting of F-actin filaments, myosin motors, and actin-binding proteins. The actomyosin cortex is attached to the cell membrane via membrane-anchoring proteins called ERM proteins that plays a central role in cell shape control. The protein constituents of the cortex undergo rapid turnover, making the cortex both mechanically rigid and highly plastic, two properties essential to its function. In most cases, the cortex is in the range of 100 to 1000 nanometers thick.

<span class="mw-page-title-main">Major sperm protein</span>

Major sperm protein (MSP) is a nematode specific small protein of 126 amino acids with a molecular weight of 14 kDa. It is the key player in the motility machinery of nematodes that propels the crawling movement/motility of nematode sperm. It is the most abundant protein present in nematode sperm, comprising 15% of the total protein and more than 40% of the soluble protein. MSP is exclusively synthesized in spermatocytes of the nematodes. The MSP has two main functions in the reproduction of the helminthes: i) as cytosolic component it is responsible for the crawling movement of the mature sperm, and ii) once released, it acts as hormone on the female germ cells, where it triggers oocyte maturation and stimulates the oviduct wall to contract to bring the oocytes into position for fertilization. MSP has first been identified in Caenorhabditis elegans.

Mark Steven Bretscher is a British biological scientist and Fellow of the Royal Society. He worked at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom and is currently retired.

<span class="mw-page-title-main">Protein filament</span> Long chain of protein monomers

In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, strength, and rigidity to the cell. When the filaments are packed up together, they are able to form three different cellular parts. The three major classes of protein filaments that make up the cytoskeleton include: actin filaments, microtubules and intermediate filaments.

When molecules on the surface of a motile eukaryotic cell are crosslinked, they are moved to one end of the cell to form a "cap". This phenomenon, the process of which is called cap formation, was discovered in 1971 on lymphocytes and is a property of amoebae and all locomotory animal cells except sperm. The crosslinking is most easily achieved using a polyvalent antibody to a surface antigen on the cell. Cap formation can be visualised by attaching a fluorophore, such as fluorescein, to the antibody.

<span class="mw-page-title-main">MACF1</span> Protein-coding gene in the species Homo sapiens

Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 is a protein that in humans is encoded by the MACF1 gene.

<span class="mw-page-title-main">Stress fiber</span> Contractile actin bundles found in non-muscle cells

Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin I (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated actomyosin structure within non-muscle cells. Stress fibers have been shown to play an important role in cellular contractility, providing force for a number of functions such as cell adhesion, migration and morphogenesis.

<span class="mw-page-title-main">Amoeboid movement</span> Mode of locomotion in eukaryotic cells

Amoeboid movement is the most typical mode of locomotion in adherent eukaryotic cells. It is a crawling-like type of movement accomplished by protrusion of cytoplasm of the cell involving the formation of pseudopodia ("false-feet") and posterior uropods. One or more pseudopodia may be produced at a time depending on the organism, but all amoeboid movement is characterized by the movement of organisms with an amorphous form that possess no set motility structures.

<span class="mw-page-title-main">Arp2/3 complex</span> Macromolecular complex

Arp2/3 complex is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton-containing eukaryotic cells. Two of its subunits, the Actin-Related Proteins ARP2 and ARP3, closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70-degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion, phagocytosis, and intracellular motility of lipid vesicles.

<span class="mw-page-title-main">FERM domain</span>

In molecular biology, the FERM domain is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus in the majority of proteins in which it is found.

Uropods, in immunology, refer to the hind part of polarized cells during cell migration that stabilize and move the cell. Polarized leukocytes move using amoeboid cell migration mechanisms, with a small leading edge, main cell body, and posterior uropod protrusion. Cytoskeleton contraction and extension, controlled by various polarized signals, helps propel the cell body forward. Leukocyte polarization is an important requirement for migration, activation and apoptosis in the adaptive and innate immune systems; most leukocytes, including monocytes, granulocytes, and T and B lymphocytes migrate to and from primary and secondary lymphoid organs to tissues to initiate immune responses to pathogens.

References

  1. ↑ Mak M, Spill F, Kamm RD, Zaman MH (February 2016). "Single-Cell Migration in Complex Microenvironments: Mechanics and Signaling Dynamics". Journal of Biomechanical Engineering. 138 (2): 021004. doi:10.1115/1.4032188. PMC   4844084 . PMID   26639083.
  2. ↑ Swaney K, Huang CH, Devreotes PN (2010). "Eukaryotic Chemotaxis: A Network of Signaling Pathways Controls Motility, Directional Sensing, and Polarity". Annual Review of Biophysics. 39: 265–289. doi:10.1146/annurev.biophys.093008.131228. PMC   4364543 . PMID   20192768.
  3. ↑ Zhan H, Bhattacharya S, Cai H, Iglesias PA, Huang CH, Devreotes PN (September 2020). "An excitable Ras/PI3K/ERK signaling network controls migration and oncogenic transformation in epithelial cells". Developmental Cell. 54 (5): 608–623. doi:10.1016/j.devcel.2020.08.001. PMC   7505206 . PMID   32877650.
  4. ↑ Huber F, Schnauß J, Rönicke S, Rauch P, Müller K, Fütterer C, et al. (January 2013). "Emergent complexity of the cytoskeleton: from single filaments to tissue". Advances in Physics. 62 (1): 1–112. Bibcode:2013AdPhy..62....1H. doi:10.1080/00018732.2013.771509. PMC   3985726 . PMID   24748680. online
  5. 1 2 Pebworth MP, Cismas SA, Asuri P (2014). "A novel 2.5D culture platform to investigate the role of stiffness gradients on adhesion-independent cell migration". PLOS ONE. 9 (10): e110453. Bibcode:2014PLoSO...9k0453P. doi: 10.1371/journal.pone.0110453 . PMC   4195729 . PMID   25310593.
  6. ↑ Prieto D, Aparicio G, Sotelo-Silveira JR (November 2017). "Cell migration analysis: A low-cost laboratory experiment for cell and developmental biology courses using keratocytes from fish scales". Biochemistry and Molecular Biology Education. 45 (6): 475–482. doi: 10.1002/bmb.21071 . PMID   28627731.
  7. ↑ Dormann D, Weijer CJ (August 2006). "Imaging of cell migration". The EMBO Journal. 25 (15): 3480–3493. doi:10.1038/sj.emboj.7601227. PMC   1538568 . PMID   16900100.
  8. ↑ Shih W, Yamada S (December 2011). "Live-cell imaging of migrating cells expressing fluorescently-tagged proteins in a three-dimensional matrix". Journal of Visualized Experiments (58). doi:10.3791/3589. PMC   3369670 . PMID   22215133.
  9. ↑ "What is Cell Migration?". Cell Migration Gateway. Cell Migration Consortium. Archived from the original on 22 October 2014. Retrieved 24 March 2013.
  10. ↑ Abercrombie M, Heaysman JE, Pegrum SM (October 1970). "The locomotion of fibroblasts in culture. 3. Movements of particles on the dorsal surface of the leading lamella". Experimental Cell Research. 62 (2): 389–398. doi:10.1016/0014-4827(70)90570-7. PMID   5531377.
  11. ↑ Willard SS, Devreotes PN (September 2006). "Signaling pathways mediating chemotaxis in the social amoeba, Dictyostelium discoideum". European Journal of Cell Biology. 85 (9–10): 897–904. doi:10.1016/j.ejcb.2006.06.003. PMID   16962888.
  12. ↑ Wang YL (August 1985). "Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling". The Journal of Cell Biology. 101 (2): 597–602. doi:10.1083/jcb.101.2.597. PMC   2113673 . PMID   4040521.
  13. ↑ Mitchison TJ, Cramer LP (February 1996). "Actin-based cell motility and cell locomotion". Cell. 84 (3): 371–379. doi: 10.1016/S0092-8674(00)81281-7 . PMID   8608590. S2CID   982415.
  14. ↑ Pollard TD, Borisy GG (February 2003). "Cellular motility driven by assembly and disassembly of actin filaments". Cell. 112 (4): 453–465. doi: 10.1016/S0092-8674(03)00120-X . PMID   12600310. S2CID   6887118.
  15. ↑ Doherty GJ, McMahon HT (2008). "Mediation, modulation, and consequences of membrane-cytoskeleton interactions". Annual Review of Biophysics. 37: 65–95. doi:10.1146/annurev.biophys.37.032807.125912. PMID   18573073.
  16. ↑ Yang H, Ganguly A, Cabral F (October 2010). "Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs". The Journal of Biological Chemistry. 285 (42): 32242–32250. doi: 10.1074/jbc.M110.160820 . PMC   2952225 . PMID   20696757.
  17. 1 2 3 Ganguly A, Yang H, Sharma R, Patel KD, Cabral F (December 2012). "The role of microtubules and their dynamics in cell migration". The Journal of Biological Chemistry. 287 (52): 43359–43369. doi: 10.1074/jbc.M112.423905 . PMC   3527923 . PMID   23135278.
  18. ↑ Bretscher MS (January 1983). "Distribution of receptors for transferrin and low density lipoprotein on the surface of giant HeLa cells". Proceedings of the National Academy of Sciences of the United States of America. 80 (2): 454–458. Bibcode:1983PNAS...80..454B. doi: 10.1073/pnas.80.2.454 . PMC   393396 . PMID   6300844.
  19. ↑ Hopkins CR, Gibson A, Shipman M, Strickland DK, Trowbridge IS (June 1994). "In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella". The Journal of Cell Biology. 125 (6): 1265–1274. doi:10.1083/jcb.125.6.1265. PMC   2290921 . PMID   7515888.
  20. ↑ Bretscher MS (November 1996). "Getting membrane flow and the cytoskeleton to cooperate in moving cells". Cell. 87 (4): 601–606. doi: 10.1016/S0092-8674(00)81380-X . PMID   8929529. S2CID   14776455.
  21. ↑ Bretscher MS (February 1992). "Circulating integrins: alpha 5 beta 1, alpha 6 beta 4 and Mac-1, but not alpha 3 beta 1, alpha 4 beta 1 or LFA-1". The EMBO Journal. 11 (2): 405–410. doi:10.1002/j.1460-2075.1992.tb05068.x. PMC   556468 . PMID   1531629.
  22. ↑ Thompson CR, Bretscher MS (September 2002). "Cell polarity and locomotion, as well as endocytosis, depend on NSF". Development. 129 (18): 4185–4192. doi:10.1242/dev.129.18.4185. PMID   12183371.
  23. ↑ Bretscher MS, Clotworthy M (August 2007). "Using single loxP sites to enhance homologous recombination: ts mutants in Sec1 of Dictyostelium discoideum". PLOS ONE. 2 (8): e724. Bibcode:2007PLoSO...2..724B. doi: 10.1371/journal.pone.0000724 . PMC   1933600 . PMID   17684569.
  24. ↑ Zanchi R, Howard G, Bretscher MS, Kay RR (October 2010). "The exocytic gene secA is required for Dictyostelium cell motility and osmoregulation". Journal of Cell Science. 123 (Pt 19): 3226–3234. doi:10.1242/jcs.072876. PMC   2939799 . PMID   20807800.
  25. ↑ Aguado-Velasco C, Bretscher MS (December 1999). "Circulation of the plasma membrane in Dictyostelium". Molecular Biology of the Cell. 10 (12): 4419–4427. doi:10.1091/mbc.10.12.4419. PMC   25767 . PMID   10588667.
  26. 1 2 3 O'Neill PR, Castillo-Badillo JA, Meshik X, Kalyanaraman V, Melgarejo K, Gautam N (July 2018). "Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode". Developmental Cell. 46 (1): 9–22.e4. doi:10.1016/j.devcel.2018.05.029. PMC   6048972 . PMID   29937389.
  27. ↑ Purcell EM (1977). "Life at Low Reynolds Number". American Journal of Physics. 45 (3): 3–11. Bibcode:1977AmJPh..45....3P. doi:10.1119/1.10903. hdl: 2433/226838 .
  28. ↑ Barry NP, Bretscher MS (June 2010). "Dictyostelium amoebae and neutrophils can swim". Proceedings of the National Academy of Sciences of the United States of America. 107 (25): 11376–11380. Bibcode:2010PNAS..10711376B. doi: 10.1073/pnas.1006327107 . PMC   2895083 . PMID   20534502.
  29. ↑ Bell GR, Collins SR (July 2018). ""Rho"ing a Cellular Boat with Rearward Membrane Flow". Developmental Cell. 46 (1): 1–3. doi: 10.1016/j.devcel.2018.06.008 . PMID   29974859.
  30. ↑ Tanaka M, Kikuchi T, Uno H, Okita K, Kitanishi-Yumura T, Yumura S (October 2017). "Turnover and flow of the cell membrane for cell migration". Scientific Reports. 7 (1): 12970. Bibcode:2017NatSR...712970T. doi:10.1038/s41598-017-13438-5. PMC   5636814 . PMID   29021607.
  31. ↑ Shellard A, Szabó A, Trepat X, Mayor R (October 2018). "Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis". Science. 362 (6412): 339–343. Bibcode:2018Sci...362..339S. doi:10.1126/science.aau3301. PMC   6218007 . PMID   30337409.
  32. 1 2 3 Coskun H, Coskun H (March 2011). "Cell physician: reading cell motion: a mathematical diagnostic technique through analysis of single cell motion". Bulletin of Mathematical Biology. 73 (3): 658–682. doi:10.1007/s11538-010-9580-x. PMID   20878250. S2CID   37036941.
  33. ↑ Banerjee T, Biswas D, Pal DS, Miao Y, Iglesias PA, Devreotes PN (October 2022). "Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration". Nature Cell Biology. 24 (10): 1499–1515. doi:10.1038/s41556-022-00997-7. PMC   10029748 . PMID   36202973. S2CID   248990694.
  34. ↑ Parent CA, Devreotes PN (April 1999). "A cell's sense of direction". Science. 284 (5415): 765–770. Bibcode:1999Sci...284..765P. doi:10.1126/science.284.5415.765. PMID   10221901.
  35. ↑ Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, et al. (December 2003). "Cell migration: integrating signals from front to back". Science. 302 (5651): 1704–1709. Bibcode:2003Sci...302.1704R. doi:10.1126/science.1092053. PMID   14657486. S2CID   16029926.
  36. ↑ Pal DS, Banerjee T, Lin Y, de Trogoff F, Borleis J, Iglesias PA, et al. (July 2023). "Actuation of single downstream nodes in growth factor network steers immune cell migration". Developmental Cell. 58 (13): 1170–1188.e7. doi:10.1016/j.devcel.2023.04.019. PMC   10524337 . PMID   37220748.
  37. ↑ Lin Y, Pal DS, Banerjee P, Banerjee T, Qin G, Deng Y, et al. (July 2024). "Ras suppression potentiates rear actomyosin contractility-driven cell polarization and migration". Nature Cell Biology: 1–15. doi:10.1038/s41556-024-01453-4. PMID   38951708.
  38. ↑ Li R, Gundersen GG (November 2008). "Beyond polymer polarity: how the cytoskeleton builds a polarized cell". Nature Reviews. Molecular Cell Biology. 9 (11): 860–873. doi:10.1038/nrm2522. PMID   18946475. S2CID   19500145.
  39. ↑ Meyer AS, Hughes-Alford SK, Kay JE, Castillo A, Wells A, Gertler FB, et al. (June 2012). "2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen". The Journal of Cell Biology. 197 (6): 721–729. doi:10.1083/jcb.201201003. PMC   3373410 . PMID   22665521.
  40. ↑ Coskun H (2006). Mathematical Models for Ameboid Cell Motility and Model Based Inverse Problems (Ph.D. thesis). University of Iowa – via ProQuest.
  41. ↑ Coskun H, Li Y, Mackey MA (January 2007). "Ameboid cell motility: a model and inverse problem, with an application to live cell imaging data". Journal of Theoretical Biology. 244 (2): 169–179. Bibcode:2007JThBi.244..169C. doi:10.1016/j.jtbi.2006.07.025. PMID   16997326.
  42. ↑ Coskun H, Coskun H (March 2011). "Cell physician: reading cell motion: a mathematical diagnostic technique through analysis of single cell motion". Bulletin of Mathematical Biology. 73 (3): 658–82. doi:10.1007/s11538-010-9580-x. PMID   20878250.; Lay summary in: "Mathematicians use cell 'profiling' to detect abnormalities -- including cancer". ScienceDaily.
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