The actomyosin cortex is an active material that provides animal cells with a strong but flexible exterior whose mechanics, including non-Gaussian fluctuations and occasional large displacements or cytoquakes, have defied explanation. We study the active fluctuations of the cortex using nanoscale tracking of arrays of flexible microposts adhered to multiple cultured cell types. When the confounding effects of static heterogeneity and tracking error are removed, the fluctuations are found to be heavy tailed and well described by a truncated Lévy-stable distribution over a wide range of timescales, in multiple cell types. The largest random displacements closely resemble the earlier-reported cytoquakes, but notably, we find these cytoquakes are not due to earthquakelike cooperative rearrangement of many cytoskeletal elements. Rather, they are indistinguishable from chance large excursions of a superdiffusive random process driven by heavy-tailed noise. The noncooperative microscopic events driving these fluctuations need not be larger than the expected elastic energy of single tensed cortical actin filaments, and the implied distribution of microscopic event energies will need to be accounted for by future models of the cytoskeleton.
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Active gels, heavy tails, and the cytoskeleton
The eukaryotic cell's cytoskeleton is a prototypical example of an active material: objects embedded within it are driven by molecular motors acting on the cytoskeleton, leading to anomalous diffusive behavior. Experiments tracking the behavior of cell-attached objects have observed anomalous diffusion with a distribution of displacements that is non-Gaussian, with heavy tails. This has been attributed to “cytoquakes” or other spatially extended collective effects. We show, using simulations and analytical theory, that a simple continuum active gel model driven by fluctuating force dipoles naturally creates heavy power-law tails in cytoskeletal displacements. We predict that this power law exponent should depend on the geometry and dimensionality of where force dipoles are distributed through the cell; we find qualitatively different results for force dipoles in a 3D cytoskeleton and a quasi-two-dimensional cortex. We then discuss potential applications of this model both in cells and in synthetic active gels.
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- Award ID(s):
- 1945141
- PAR ID:
- 10325813
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 17
- Issue:
- 43
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 9876 to 9892
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Long-term temporal correlations in time series in a form of an event sequence have been characterized using an autocorrelation function that often shows a power-law decaying behavior. Such scaling behavior has been mainly accounted for by the heavy-tailed distribution of interevent times, i.e., the time interval between two consecutive events. Yet, little is known about how correlations between consecutive interevent times systematically affect the decaying behavior of the autocorrelation function. Empirical distributions of the burst size, which is the number of events in a cluster of events occurring in a short time window, often show heavy tails, implying that arbitrarily many consecutive interevent times may be correlated with each other. In the present study, we propose a model for generating a time series with arbitrary functional forms of interevent time and burst size distributions. Then, we analytically derive the autocorrelation function for the model time series. In particular, by assuming that the interevent time and burst size are power-law distributed, we derive scaling relations between power-law exponents of the autocorrelation function decay, interevent time distribution, and burst size distribution. These analytical results are confirmed by numerical simulations. Our approach helps to rigorously and analytically understand the effects of correlations between arbitrarily many consecutive interevent times on the decaying behavior of the autocorrelation function.
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The cell cytoskeleton is a dynamic assembly of semi-flexible filaments and motor proteins. The cytoskeleton mechanics is a determining factor in many cellular processes, including cell division, cell motility and migration, mechanotransduction and intracellular transport. Mechanical properties of the cell, which are determined partly by its cytoskeleton, are also used as biomarkers for disease diagnosis and cell sorting. Experimental studies suggest that in whole cell scale, the cell cytoskeleton and its permeating cytosol may be modelled as a two-phase poro-viscoelastic (PVE) material composed of a viscoelastic (VE) network permeated by a viscous cytosol. We present the first general solution to this two-phase system in spherical coordinates, where we assume that both the fluid and network phases are in their linear response regime. Specifically, we use generalized linear incompressible and compressible VE constitutive equations to describe the stress in the fluid and network phases, respectively. We assume a constant permeability that couples the fluid and network displacements. We use these general solutions to study the motion of a rigid sphere moving under a constant force inside a two-phase system, composed of a linear elastic network and a Newtonian fluid. It is shown that the network compressibility introduces a slow relaxation of the sphere and non-monotonic network displacements with time along the direction of the applied force. Our results can be applied to particle-tracking microrheology to differentiate between PVE and VE materials, and to measure the fluid permeability as well as VE properties of the fluid and the network phases.more » « less
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Living cells are out of equilibrium active materials. Cell-generated forces are transmitted across the cytoskeleton network and to the extracellular environment. These active force interactions shape cellular mechanical behavior, trigger mechano-sensing, regulate cell adaptation to the microenvironment and can affect disease outcomes. In recent years, the mechanobiology community has witnessed the emergence of many experimental and theoretical approaches to study cells as mechanically active materials. In this review, we highlight recent advancements in incorporating active characteristics of cellular behavior at different length scales into classic viscoelastic models by either adding an active tension-generating element or by adjusting the resting length of an elastic element in the model. Summarizing the two groups of approaches, we will review the formulation, and application of these models to understand cellular adaptation mechanisms in response to various types of mechanical stimuli, such as the effect of extracellular matrix properties and external loadings or deformations.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D1SM00705J
