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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 $\alpha$-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. 

Many soft and biological materials display so-called ‘soft glassy’ dynamics; their constituents undergo anomalous random motions and complex cooperative rearrangements. A recent simulation model of one soft glassy material, a coarsening foam, suggested that the random motions of its bubbles are due to the system configuration moving over a fractal energy landscape in high-dimensional space. Here we show that the salient geometrical features of such high-dimensional fractal landscapes can be explored and reliably quantified, using empirical trajectory data from many degrees of freedom, in a model-free manner. For a mayonnaise-like dense emulsion, analysis of the observed trajectories of oil droplets quantitatively reproduces the high-dimensional fractal geometry of the configuration path and its associated local energy minima generated using a computational model. That geometry in turn drives the droplets’ complex random motion observed in real space. Our results indicate that experimental studies can elucidate whether the similar dynamics in different soft and biological materials may also be due to fractal landscape dynamics. 

The mechanical behavior of soft collagenous tissues is largely influenced by the reinforcing collagen fiber microstructure. The anisotropic collagen microstructure can remodel in response to changes in mechanical loading, which can dramatically alter the mechanical properties of the tissues and the mechanical environment of the resident cells. It is important to study the remodeling mechanisms of collagen tissues to understand the pathophysiology of various connective tissue diseases. We hypothesize that the collagen structure actively changes in response to mechanical stimuli through concurrent processes of collagen deposition and degradation and that the rates of these processes are altered by collagen mechanochemistry, mechanosensitive collagen production, and cellular contraction. In prior studies, we developed micromechanical models of collagen tissues to investigate the role of collagen mechanochemistry and mechanosensitive collagen production in remodeling the collagen fiber structure and tissue growth.[1,2] We found that stress inhibition of enzymatic degradation and stimulation of collagen production can explain many phenomena, including remodeling the anisotropic collagen structure along the directions of the maximum principal stress and the development of stress homeostasis. The goal of this study is to investigate the effect of mechanical loading on the active behavior of the cells. Our approach uses a model 3D microtissue systems, self-assembled on a magnetically actuated two-pillar system (µTUG), to investigate these cell-collagen interactions and effects of mechanical loading. The micropillar support allows for measurement of the active cellular contraction, while the magnetic tweezer allows for mechanical testing of the microtissue under a controlled stress rate. Digital image analysis is applied to measure the local two-dimensional (2D) strain field. To analyze the mechanical measurements for mechanical properties of the collagen structure and active behavior of the cells, we developed a micromechanical model for the mechanical behavior of the microtissue. The micromechanical model includes the elastic behavior of the anisotropic collagen structure and the anisotropic active behavior of the cells. To describe mechanosensitive cellular contraction, we assume concurrent polymerization/depolymerization of actin filaments, where the polymerization rate increases with the fiber stress. In this paper, we will briefly summarize the model and describe an initial model validation by comparing to µTUG experiments measuring the stress-strain behavior of the microtissue to load-unload tests. 

Abstract The actomyosin cytoskeleton enables cells to resist deformation, crawl, change their shape and sense their surroundings. Despite decades of study, how its molecular constituents can assemble together to form a network with the observed mechanics of cells remains poorly understood. Recently, it has been shown that the actomyosin cortex of quiescent cells can undergo frequent, abrupt reconfigurations and displacements, called cytoquakes. Notably, such fluctuations are not predicted by current physical models of actomyosin networks, and their prevalence across cell types and mechanical environments has not previously been studied. Using micropost array detectors, we have performed high-resolution measurements of the dynamic mechanical fluctuations of cells’ actomyosin cortex and stress fiber networks. This reveals cortical dynamics dominated by cytoquakes—intermittent events with a fat-tailed distribution of displacements, sometimes spanning microposts separated by 4 μm, in all cell types studied. These included 3T3 fibroblasts, where cytoquakes persisted over substrate stiffnesses spanning the tissue-relevant range of 4.3 kPa–17 kPa, and primary neonatal rat cardiac fibroblasts and myofibroblasts, human embryonic kidney cells and human bone osteosarcoma epithelial (U2OS) cells, where cytoquakes were observed on substrates in the same stiffness range. Overall, these findings suggest that the cortex self-organizes into a marginally stable mechanical state whose physics may contribute to cell mechanical properties, active behavior and mechanosensing.