Cytoskeletal prestress homeostasis proposed as the biological principle of living cells

A landmark review by Prof. Wang from Northeastern University puts forward an innovative core viewpoint: besides the Central Dogma of molecular biology and metabolic regulation, cytoskeletal (CSK) prestress homeostasis serves as the third fundamental biological principle universally existing across all living species, ranging from bacteria, archaea, protists and plant cells to mammalian somatic cells.

The authors systematically summarized abundant experimental evidence to verify that endogenous cytoskeletal pre-existing tensile stress is dynamically maintained within a physiological range. This homeostasis dominates multiple core cellular behaviors, including cell stiffness modulation, long-distance intracellular force transmission, rapid cytoplasmic mechanotransduction, chromatin stretching-mediated gene transcription, nuclear mechanical memory, stem cell differentiation, tumor cell malignant transformation and metabolism reprogramming. Unlike self-assembly and tensegrity (physical rules also found in non-living materials), CSK prestress homeostasis relies on ATP-powered active cytoskeleton contraction and biological feedback loops, which exclusively emerge in living organisms.

For academic researchers and biotech developers, this groundbreaking theory brings huge translational value: dysregulated prestress homeostasis is closely linked to cellular senescence, fibrosis, cancer metastasis and developmental malformations. Targeted pharmacological modulation of cytoskeletal prestress opens up brand-new directions for novel drug screening, tumor intervention, anti-senescence development and engineered organoid construction.

Interested teams can explore novel mechanomedicine pipelines based on the principle and develop mechanical-targeted therapeutic strategies for unmet clinical demands.