Collective dynamics of actomyosin cortex endow cells with intrinsic mechanosensing properties

Living cells adapt and respond actively to the mechanical properties of their environment. In addition to biochemical mechanotransduction, evidence exists for a myosin-dependent, purely mechanical sensitivity to the stiffness of the surroundings at the scale of the whole cell. Using a minimal model of the dynamics of actomyosin cortex, we show that the interplay of myosin power strokes with the rapidly remodelling actin network results in a regulation of force and cell shape that adapts to the stiffness of the environment. Instantaneous changes of the environment stiffness are found to trigger an intrinsic mechanical response of the actomyosin cortex. Cortical retrograde flow resulting from actin polymerisation at the edges is shown to be modulated by the stress resulting from myosin contractility, which in turn regulates the cell size in a force-dependent manner. The model describes the maximum force that cells can exert and the maximum speed at which they can contract, which are measured experimentally. These limiting cases are found to be associated with energy dissipation phenomena which are of the same nature as those taking place during the contraction of a whole muscle. This explains the fact that single nonmuscle cell and whole muscle contraction both follow a Hill-like force-velocity relationship

How the cell got its shape : A visco-elasto-active model of the cytoskeleton

Living cells cytoskeleton is made of polymers which are constantly being re-modelled by polymerisation and depolymerisation, and which are bound to one another (crosslinked) through even more unstable molecules, lasting for about one second. With such a dynamic structure, one may wonder how cells can maintain a given shape over time ranges several orders of magnitude larger than the turn-over time of their constituents. We propose a rheological model which features crosslink turn-over, polymerisation and molecular motor-generated contractile forces, and provides answers to these questions

Power laws in microrheology experiments on living cells: comparative analysis and modelling

We compare and synthesize the results of two microrheological experiments on the cytoskeleton of single cells. In the first one, the creep function J(t) of a cell stretched between two glass plates is measured after applying a constant force step. In the second one, a micrometric bead specifically bound to transmembrane receptors is driven by an oscillating optical trap, and the viscoelastic coefficient $G_e(\omega)$ is retrieved. Both $J(t)$ and $G_e(\omega)$ exhibit power law behavior: $J(t)= A(t/t_0)^\alpha$ and $\bar G_e(\omega)\bar = G_0 (\omega/\omega_0)^\alpha$, with the same exponent $\alpha\approx 0.2$. This power law behavior is very robust ; $\alpha$ is distributed over a narrow range, and shows almost no dependance on the cell type, on the nature of the protein complex which transmits the mechanical stress, nor on the typical length scale of the experiment. On the contrary, the prefactors $A_0$ and $G_0$appear very sensitive to these parameters. Whereas the exponents $\alpha$ are normally distributed over the cell population, the prefactors $A_0$ and $G_0$ follow a log-normal repartition. These results are compared with other data published in the litterature. We propose a global interpretation, based on a semi-phenomenological model, which involves a broad distribution of relaxation times in the system. The model predicts the power law behavior and the statistical repartition of the mechanical parameters, as experimentally observed for the cells. Moreover, it leads to an estimate of the largest response time in the cytoskeletal network: $\tau_m \approx 1000$ s.Comment: 47 pages, 14 figures // v2: PDF file is now Acrobat Reader 4 (and up) compatible // v3: Minor typos corrected - The presentation of the model have been substantially rewritten (p. 17-18), in order to give more details - Enhanced description of protocols // v4: Minor corrections in the text : the immersion angles are estimated and not measured // v5: Minor typos corrected. Two references were clarifie

Rhéologie à l' échelle d' une cellule vivante

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

The mechanics behind cell polarity

International audienceThe generation of cell polarity is one of the most intriguing symmetry-breaking events in biology. It is involved in almost all physiological and developmental processes and, despite the differences between plant and animal cell structures, cell polarity is generated by a similar core mechanism that comprises the extracellular matrix (ECM), Rho GTPase, the cytoskeleton, and the membranes. Several recent articles show that mechanical factors also contribute to the establishment and robustness of cell polarity, and the different molecular actors of cell polarity are now viewed as integrators of both biochemical and mechanical signals. Although cell polarity remains a complex process, some level of functional convergence between plants and animals is revealed. Following comparative presentation of cell polarity in plants and animals, we will discuss the theoretical background behind the role of mechanics in polarity and the relevant experimental tests, focusing on ECM anchorage, cytoskeleton behavior, and membrane tension

Microplates-based rheometer for a single living cell

International audienceWe developed a new versatile micron-scale rheometer allowing us to measure the creep or the relaxation function (time analysis), as well as to determine the dynamical complex modulus (frequency analysis) of a single living cell. In this setup, a microscopic sample can be stretched or compressed uniaxially between two parallel microplates: one rigid, the other flexible. The flexible microplate is used as a nanonewton force sensor of calibrated stiffness, the force being simply proportional to the plate deflection. An original design of the microplates allows us to achieve an efficient feedback control of either strain or stress applied to the cell. Controlling the flexible plate deflection with a typical precision of less than 200nm, we are able to apply stresses ranging from a few pascals to thousands of pascals with a precision better than 2%. The control of the flexible plate deflexion is achieved by direct imaging of the plate tip on a photosensitive detector mounted on the phototube of an inverted microscope. Thus, the detection principle is suitable to all usual microscopes and very easy to set up. Beyond the creep function, already analyzed in detail in a previous work, we report here the first measurement of the relaxation function, as well as of the storage and the loss dynamic moduli [G′(f) and G′′(f), f ranging from 0.02to10Hz] for an isolated living cell. Eventually, the rheometer we built is not limited to cell stretching. It should also be a powerful tool to study the rheology of micron sized samples such as microgels or vesicles, as well as to perform shear experiments

Microrheology of living cells at different time and length scales

Chapter 1International audienc