Cell mechanics is a sub-field of biophysics that focuses on the mechanical properties and behavior of living cells and how it relates to cell function. [1] It encompasses aspects of cell biophysics, biomechanics, soft matter physics and rheology, mechanobiology and cell biology.
Eukaryotic cells [2] are cells that consist of membrane-bound organelles, a membrane-bound nucleus, and more than one linear chromosome. Being much more complex than prokaryotic cells, cells without a true nucleus, eukaryotes must protect its organelles from outside forces.
Plant cell mechanics combines principles of biomechanics and mechanobiology to investigate the growth and shaping of the plant cells. Plant cells, similar to animal cells, respond to externally applied forces, such as by reorganization of their cytoskeletal network. The presence of a considerably rigid extracellular matrix, the cell wall, however, bestows the plant cells with a set of particular properties. Mainly, the growth of plant cells is controlled by the mechanics and chemical composition of the cell wall. [3] A major part of research in plant cell mechanics is put toward the measurement and modeling of the cell wall mechanics to understand how modification of its composition and mechanical properties affects the cell function, growth and morphogenesis. [4] [5]
Because animal cells [6] do not have cell walls to protect them like plant cells, they require other specialized structures to sustain external mechanical forces. All animal cells are encased within a cell membrane made of a thin lipid bilayer that protects the cell from exposure to the outside environment. Using receptors composed of protein structures, the cell membrane is able to let selected molecules within the cell. Inside the cell membrane includes the cytoplasm, which contains the cytoskeleton. [7] A network of filamentous proteins including microtubules, intermediate filaments, and actin filaments makes up the cytoskeleton and helps maintain the cell's shape. By working together, the three types of polymers can organize themselves to counter the applied external forces and resist deformation. However, there are differences between the three polymers.
The primary structural component of the cytoskeleton is actin filaments. Being the narrowest with a diameter of 7 nm and most flexible out of the three types of polymers, actin filaments are typically found at the very edge of the cytoplasm in animal cells. [1] Formed by the linking of polymers of a protein called actin, they help give cells shape and structure and are able to transport protein packages and organelles. Furthermore, actin filaments have the ability to be assembled and disassembled quickly, allowing them to take part in cell mobility. [8]
On the other hand, intermediate filaments are more permanent structures with a diameter of 8 to 10 nm. [9] Composed of numerous fibrous protein strands wound together, intermediate proteins’ main role is bearing tension and retaining the shape and structure of the cell by securing the nucleus and other organelles in their designated areas.
The largest cytoskeletal structure of the three types of polymers is the microtubules with a diameter of 25 nm. [8] Unlike actin filaments, microtubules are stiff, hollow structures that radiate outwards from the microtubule organizing center (MTOC). Composed of tubulin proteins, microtubules are dynamic structures that allows them to shrink or grow with the addition or removal of tubulin proteins. In terms of cell mechanics, microtubules’ main purpose is to resist compressive cellular forces and act as a transportation system for motor proteins. [8]
It was shown that melanin also can have an impact on mechanic properties of cells. The research done by Sarna's team proved that heavily pigmented melanoma cells have Young's modulus about 4.93, when in non-pigmented ones it was only 0.98. [10] In another experiment they found that elasticity of melanoma cells is important for its metastasis and growth: non-pigmented tumors were bigger than pigmented and it was much easier for them to spread. They shown that there are both pigmented and non-pigmented cells in melanoma tumors, so that they can both be drug-resistant and metastatic. [10]
Because cells are tiny, soft objects that must be measured differently than materials like metal, plastic, and glass, new techniques have been developed for the accurate measurement of cell mechanics. The variety of techniques can be divided into two categories: force application techniques and force sensing techniques. [1] In case of walled cells, such as plant or fungal cells, due to existence of a stiff, anisotropic and curved cell wall encapsulating the cells, special considerations and tailored approaches may be required compared to the methods used to measure the mechanics of animal cells. [11]
Force application techniques uses the cell's response of deformation to force applied onto the cell as a way to measure cell mechanical properties. [12] There are several different types of force application techniques including:
Researchers who study cell mechanics are interested in the mechanics and dynamics of the assemblies and structures that make up the cell including membranes, cytoskeleton, organelles, and cytoplasm, and how they interact to give rise to the emergent properties of the cell as a whole. [22]
A particular focus of many cell mechanical studies has been the cytoskeleton, which (in animal cells) can be thought to consist of:
The active non-equilibrium and non-linear rheological properties of cellular assemblies have been keen point of research in recent times. [23] [24] Another point of interest has been how cell cycle-related changes in cytoskeletal activity affect global cell properties, such as intracellular pressure increase during mitotic cell rounding. [25]
In cell biology, the cytoplasm describes all material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main components of the cytoplasm are the cytosol, the organelles, and various cytoplasmic inclusions. The cytoplasm is about 80% water and is usually colorless.
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.
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 and or disassembly depending on the cell's requirements.
Cytokinesis is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.
A pollen tube is a tubular structure produced by the male gametophyte of seed plants when it germinates. Pollen tube elongation is an integral stage in the plant life cycle. The pollen tube acts as a conduit to transport the male gamete cells from the pollen grain—either from the stigma to the ovules at the base of the pistil or directly through ovule tissue in some gymnosperms. In maize, this single cell can grow longer than 12 inches (30 cm) to traverse the length of the pistil.
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm.
FtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of bacterial cell division. FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamenting temperature-sensitive mutant Z." The hypothesis was that cell division mutants of E. coli would grow as filaments due to the inability of the daughter cells to separate from one another. FtsZ is found in almost all bacteria, many archaea, all chloroplasts and some mitochondria, where it is essential for cell division. FtsZ assembles the cytoskeletal scaffold of the Z ring that, along with additional proteins, constricts to divide the cell in two.
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. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. 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.
Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mechanical work; for example, many protein-based molecular motors harness the chemical free energy released by the hydrolysis of ATP in order to perform mechanical work. In terms of energetic efficiency, this type of motor can be superior to currently available man-made motors. One important difference between molecular motors and macroscopic motors is that molecular motors operate in the thermal bath, an environment in which the fluctuations due to thermal noise are significant.
Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.
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 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.
In molecular biology, treadmilling is a phenomenon observed within protein filaments of the cytoskeletons of many cells, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks, resulting in a section of filament seemingly "moving" across a stratum or the cytosol. This is due to the constant removal of the protein subunits from these filaments at one end of the filament, while protein subunits are constantly added at the other end. Treadmilling was discovered by Wegner, who defined the thermodynamic and kinetic constraints. Wegner recognized that: “The equilibrium constant (K) for association of a monomer with a polymer is the same at both ends, since the addition of a monomer to each end leads to the same polymer.”; a simple reversible polymer can’t treadmill; ATP hydrolysis is required. GTP is hydrolyzed for microtubule treadmilling.
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.
The mechanome consists of the body, or ome, of data including cell and molecular processes relating to force and mechanical systems at molecular, cellular and tissue length scales - the fundamental "machine code" structures of the cell. The mechanome encompasses biological motors, like kinesin, myosin, RNAP, and Ribosome mechanical structures, like actin or the cytoskeleton and also proteomic and genomic components that are mechanosensitive and are involved in the response of cells to externally applied force.
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.
Nanobiomechanics is a field in nanoscience and biomechanics that combines the powerful tools of nanomechanics to explore fundamental science of biomaterials and biomechanics.
The LINC complex is a protein complex associated with both inner and outer membranes of the nucleus. It is composed of SUN-domain proteins and KASH-domain proteins. The SUN-domain proteins are associated with both nuclear lamins and chromatin and cross the inner nuclear membrane. They interact with the KASH domain proteins in the perinuclear (lumen) space between the two membranes. The KASH domain proteins cross the outer nuclear membrane and interact with actin filaments, microtubule filaments, intermediate filaments, centrosomes and cytoplasmic organelles. The number of SUN-domain and KASH-domain proteins increased in evolution.
Force Spectrum Microscopy (FSM) is an application of active microrheology developed to measure aggregate random forces in the cytoplasm. Large, inert flow tracers are injected into live cells and become lodged inside the cytoskeletal mesh, wherein it is oscillated by repercussions from active motor proteins. The magnitude of these random forces can be inferred from the frequency of oscillation of tracer particles. Tracking the fluctuations of tracer particles using optical microscopy can isolate the contribution of active random forces to intracellular molecular transport from that of Brownian motion.
Intracellular transport is the movement of vesicles and substances within a cell. Intracellular transport is required for maintaining homeostasis within the cell by responding to physiological signals. Proteins synthesized in the cytosol are distributed to their respective organelles, according to their specific amino acid’s sorting sequence. Eukaryotic cells transport packets of components to particular intracellular locations by attaching them to molecular motors that haul them along microtubules and actin filaments. Since intracellular transport heavily relies on microtubules for movement, the components of the cytoskeleton play a vital role in trafficking vesicles between organelles and the plasma membrane by providing mechanical support. Through this pathway, it is possible to facilitate the movement of essential molecules such as membrane‐bounded vesicles and organelles, mRNA, and chromosomes.