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Eukaryotic cells are mechanically supported by a polymer network called the cytoskeleton, which consumes chemical energy to dynamically remodel its structure. Recent experiments in vivo have revealed that this remodeling occasionally happens through anomalously large displacements, reminiscent of earthquakes or avalanches. These cytoskeletal avalanches might indicate that the cytoskeleton’s structural response to a changing cellular environment is highly sensitive, and they are therefore of significant biological interest. However, the physics underlying “cytoquakes” is poorly understood. Here, we use agent-based simulations of cytoskeletal self-organization to study fluctuations in the network’s mechanical energy. We robustly observe non-Gaussian statistics and asymmetrically large rates of energy release compared to accumulation in a minimal cytoskeletal model. The large events of energy release are found to correlate with large, collective displacements of the cytoskeletal filaments. We also find that the changes in the localization of tension and the projections of the network motion onto the vibrational normal modes are asymmetrically distributed for energy release and accumulation. These results imply an avalanche-like process of slow energy storage punctuated by fast, large events of energy release involving a collective network rearrangement. We further show that mechanical instability precedes cytoquake occurrence through a machine-learning model that dynamically forecasts cytoquakesmore »using the vibrational spectrum as input. Our results provide a connection between the cytoquake phenomenon and the network’s mechanical energy and can help guide future investigations of the cytoskeleton’s structural susceptibility.« less

Most mammalian cells make both β- and γ-actin, two proteins which shape the cell’s internal skeleton and its ability to migrate. The molecules share over 99% of their sequence, yet they play distinct roles. In fact, deleting the β-actin gene in mice causes death in the womb, while the animals can survive with comparatively milder issues without their γ-actin gene. How two similar proteins can have such different biological roles is a long-standing mystery. A closer look could hold some clues: β- and γ-actin may contain the same blocks (or amino acids), but the genetic sequences that encode these proteins differ by about 13%. This is because different units of genetic information – known as synonymous codons – can encode the same amino acid. These ‘silent substitutions’ have no effect on the sequence of the proteins, yet a cell reads synonymous codons (and therefore produces proteins) at different speeds. To find out the impact of silent substitutions, Vedula et al. swapped the codons for the two proteins, forcing mouse cells to produce β-actin using γ-actin codons, and vice versa. Cells with non-manipulated γ-actin and those with β-actin made using γ-actin codons could move much faster than cells with β-actin. Thismore »suggested that silent substitutions were indeed affecting the role of the protein. Vedula et al. found that cells read γ-codons – and therefore made γ-actin – much more slowly than β-codons: this also affected how quickly the protein could be dispatched where it was needed in the cell. Slower production meant that bundles of γ-actin were shorter, which allowed cells to move faster by providing a weaker anchoring system. Overall, this work provides new links between silent substitutions and protein behavior, a relatively new research area which is likely to shed light on other protein families.« less

Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. Whether and how nucleosome variants encode unique mechanical properties to their cognate chromatin structures remains elusive. Here, using in silico and in vitro nanoindentation methods, extending to in vivo dissections, we report that histone variant nucleosomes are intrinsically more elastic than their canonical counterparts. Furthermore, binding proteins, which discriminate between histone variant nucleosomes, suppress this innate elasticity and also compact chromatin. Interestingly, when we overexpress the binding proteins in vivo, we also observe increased compaction of chromatin enriched for histone variant nucleosomes, correlating with diminished access. Taken together, these data suggest a plausible link between innate mechanical properties possessed by histone variant nucleosomes, the adaptability of chromatin states in vivo, and the epigenetic plasticity of the underlying locus.