Metabolic starvation-induced cell swelling drives solid stress in tumors.

ABSTRACT: Solid stress shapes tumor growth, invasion, and therapeutic response, yet its physical origin and clinical relevance remain unclear. Here, we develop a mechano-electro-osmotic model integrating metabolic gradients, ion transport, and cellular mechanics to explain residual solid stress emergence in tumor spheroids, common models of solid tumors. We show that solid stress arises predominantly from osmotic cell swelling driven by metabolic deprivation and ion accumulation, rather than proliferation. This mechanism generates a characteristic stress architecture: isotropic compression in the hypoxic core balanced by peripheral tangential tension, causing pronounced cell and nuclear deformation. The resulting nuclear strain provides a mechanical basis for DNA damage and genomic instability impli

SUBMITTER: Dehghany M 

PROVIDER: S-EPMC12889691 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature