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Significance Tumor progression to enable metastasis includes remodeling the wavy bundles of collagen making up the tissue stromal extracellular matrix (ECM) into straight bundles within the tumor microenvironment. While wavy collagen bundles are thought to be inhibitory to cell polarization and migration in tissue, straight ECM fibers are thought to be conducive, thereby mediating metastasis. We used nanofabricated cell culture substrates that mimic the ECM fiber waveforms seen in both benign- and metastases-promoting tumor ECMs. Large amplitude ECM waves depolarized tumor cells and decreased directional migration via cell contractility-mediated organization of the cytoskeleton and adhesions. Thus, ECM architecture of normal tissue and benign tumors may generally inhibit tumor cell exit, but this may be overcome by increasing tumor cell contractility. 

Spatial mobility of chromatin-bound transcriptional regulators is intimately coupled with their dwell times and function. 

In most eukaryotic cells, actin filaments assemble into a shell-like actin cortex under the plasma membrane, controlling cellular morphology, mechanics, and signaling. The actin cortex is highly polymorphic, adopting diverse forms such as the ring-like structures found in podosomes, axonal rings, and immune synapses. The biophysical principles that underlie the formation of actin rings and cortices remain unknown. Using a molecular simulation platform called MEDYAN, we discovered that varying the filament treadmilling rate and myosin concentration induces a finite size phase transition in actomyosin network structures. We found that actomyosin networks condense into clusters at low treadmilling rates or high myosin concentrations but form ring-like or cortex-like structures at high treadmilling rates and low myosin concentrations. This mechanism is supported by our corroborating experiments on live T cells, which exhibit ring-like actin networks upon activation by stimulatory antibody. Upon disruption of filament treadmilling or enhancement of myosin activity, the pre-existing actin rings are disrupted into actin clusters or collapse towards the network center respectively. Our analyses suggest that the ring-like actin structure is a preferred state of low mechanical energy, which is, importantly, only reachable at sufficiently high treadmilling rates.