Biology subjects

Amitrano, A.

Publications and source records attributed to Amitrano, A..

3 recordsLinked to original sources

bioRxiv2026

Mechanochemical cues control the coupling of metabolic and migratory patterns in cancer

Confined migration is essential for metastasis, yet how cells adapt their migratory and metabolic programs across stiffness-varying microenvironments remains unclear. We uncover a stiffness-dependent mechano-metabolic switch governing migration. In stiff microchannels, cells utilize the osmotic engine model (OEM), relying on NHE1 activity, front-polarization, and glycolysis. In soft microchannels, migration is OEM-independent and requires pyruvate-fueled oxidative phosphorylation (OxPHOS). This OxPHOS-driven motility depends on Arp3, {beta}1-integrin and integrin-linked kinase, which increase membrane tension in confinement that in turn triggers TRPM7-mediated calcium influx and RhoA-/myosin-II contractility. Activating and polarizing NHE1, via overexpression, hypoxia or elevated viscosity, restore OEM- and glycolysis-dependent migration in soft microchannels, bypassing the need for actin polymerization in vitro and in chick embryos. Mitochondria addition reinstates Arp3 polarization and enhances migration in NHE1-overexpressing cells, enabling engagement of both mechanisms in vitro and in zebrafish. These findings uncover a previously unrecognized mechano-metabolic link, revealing that intracellular rewiring overrides stiffness-dependent metabolic demands.

cell biology↗

bioRxiv2026

Acute priming using elevated fluid viscosity recovers young-like single-cellsurveillance behaviors in aged human T cells

Aging is a complex biological process, often characterized by increased vulnerability to disease, infection, and death. This increased vulnerability is mechanistically linked to a progressive and functional decline of the immune system. In humans, aged lymphocytes lose their capacity to effectively surveil within diverse microenvironments, decreasing their capability for clearing infections and maintaining physiological homeostasis. However, specific mechanisms by which aged lymphocytes, specifically T cells, lose this capacity to surveil remain unclear. We profiled three core characteristics of T cell surveillance at single-cell resolution, specifically migration, deformability, and sensing. While aged T cells retained their capacity for spontaneous migration, they exhibited impaired cellular deformability and deficiencies in sensing local signaling cues. To modulate this surveillance defect, we performed mechanical reprogramming using elevated fluid viscosity. Results showed that acute priming of aged T cells with elevated fluid viscosity recovered a transient young-like surveillance phenotype, which was mechanistically linked to membrane tension, cortical F-actin, and Arp3 expression. These findings reveal a key source of surveillance defects in aged T cells and provide an effective mechanical approach to tuning their single-cell behaviors. TeaserRecovery of young-like surveillance phenotypes in aging human T cells via viscosity priming

bioengineering↗

bioRxiv2025

Chemical Compensation to Mechanical Loss in CellMechanosensation

Mammalian cells sense and respond to environmental changes using a complex and intelligent system that integrates chemical and mechanical signals. The transduction of mechanical cues into chemical changes modulates cell physiology, allowing a cell to adapt to its microenvironment. Understanding how the chemical and mechanical regulatory modules interact is crucial for elucidating mechanisms of mechanosensation and cellular homeostasis. In this study, we find that cells exhibit non-monotonic changes in cell volume and intracellular pH when subjected to physical stimuli and varying degrees of actomyosin cytoskeleton disruption. We discover that these non-monotonic responses are mediated by a chemical compensation mechanism, where the attenuation of actomyosin activity stimulates the activity of PI3K/Akt pathway. This, in turn, activates sodium-hydrogen exchanger 1 (NHE1), resulting in elevated intracellular pH and increased cell volume. Furthermore, we identify a competitive interaction between the PI3K/Akt and MAPK/ERK pathways - two major regulators of cell proliferation and motility. This competition modulates the chemical compensation based on the relative activities of these pathways. Our mathematical modeling reveals the network structure that is essential for establishing the non-monotonic response. Interestingly, this regulatory system is altered in HT1080 fibrosarcoma, highlighting a potential mechanistic divergence in cancer cells in contrast to their normal-like counterpart, such as NIH 3T3 and HFF-1 fibroblasts. Overall, our work reveals a compensatory mechanism between chemical and mechanical signals, providing a novel infrastructure to elucidate the integrated mechanochemical response to environmental stimuli.

biophysics↗