High-Throughput Mechanomic Screening Reveals Novel Regulators of Single-Cell Mechanics
Laura Strampe,
Katarzyna Plak,
Christine Schweitzer,
Cornelia Liebers,
Paul Müller,
Marta Urbanska,
Martin Kräter,
Buzz Baum,
Jona Kayser, et al.
Biophysical Journal
125
1-14
(2026)
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The mechanical properties of cells are dynamic, allowing them to adjust to different needs in different biological contexts. In recent years, advanced biophysical techniques have enabled the rapid, high-throughput assessment of single-cell mechanics, providing new insights into the regulation of the mechanical cell phenotype. However, the molecular mechanisms by which cells maintain and regulate their mechanical properties remain poorly understood. Here, we present a genome-scale RNA interference (RNAi) screen investigating the roles of kinase and phosphatase genes in regulating single-cell mechanics using Real-Time Fluorescence and Deformability Cytometry (RT-FDC). Our screen identified 82 known and novel mechanical regulators across diverse cellular functions from 214 targeted genes, leveraging RT-FDC’s unique capabilities for comprehensive, high-throughput mechanical phenotyping with single-cell and cell cycle resolution. These findings refine our understanding of how signaling pathways coordinate structural determinants of cell mechanical phenotypes and provide a starting point for uncovering new molecular targets involved in biomechanical regulation across diverse biological systems.
Contact
Cell Physics Division Prof. Vahid Sandoghdar Acting Division Head
Max Planck Institute for the Science of Light Staudtstr. 2 91058 Erlangen, Germany