biostudies-literatureUnknownDu HNIDDK NIH HHSNIA NIH HHSNIH HHSCells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-β-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (approximately 3 GPa) substrates, followed by senescence induction using doxorubicin, we identifiebioRxiv : the preprint server for biology2024.11.18.623471https://www.ebi.ac.uk/biostudies/studies/S-EPMC11601487biostudies-literatureSubstrate Stiffness Dictates Unique Doxorubicin-induced Senescence-associated Secretory Phenotypes and Transcriptomic Signatures in Human Pulmonary Fibroblasts.PMC11601487P30 AG068345R01 DK128435S10 OD016281S10 OD028654U01 AG060906T32 AG000266Chen NManwaring-Mueller MNagy AChang VBasisty NValentino TRWu FSchilling BBurton JBGuo LBons JWiner SMakhijani PCampisi JDu HWiner DAFurman DRose JPfalseSubstrate Stiffness Dictates Unique Doxorubicin-induced Senescence-associated Secretory Phenotypes and Transcriptomic Signatures in Human Pulmonary Fibroblasts.Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-β-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (approximately 3 GPa) substrates, followed by senescence induction using doxorubicin, we identifie2024-01-01T00:00:00Z2024 Nov2026-04-07T14:53:36.275Z2025-04-06T15:06:28.228ZS-EPMC116014873960557910.1101/2024.11.18.623471