Biology subjects

Sergides, M.

Publications and source records attributed to Sergides, M..

3 recordsLinked to original sources

bioRxiv2026

Extracellular Matrix Stiffness Controls Actin Cytoskeletal Tension

Mechanical properties of the extracellular matrix (ECM) regulate cell behavior and strongly impact the cytoskeleton, yet direct measurements of actin tension across different ECM stiffnesses are lacking. Using a genetically encoded FRET-based actin tension sensor, we show that cells cultured on stiffer substrates exhibit increased spreading, reduced multicellular aggregation, and higher molecular tension within filamentous actin. Complementary measurements using an -actinin tension sensor support increased cytoskeletal mechanical loading. These results provide direct evidence that ECM stiffness modulates intracellular actin tension during mechanotransduction.

biophysics↗

bioRxiv2021

Probing mechanotransduction in living cells by optical tweezers and FRET-based molecular force microscopy

Cells sense mechanical signals and forces to probe the external environment and adapt to tissue morphogenesis, external mechanical stresses, and a wide range of diverse mechanical cues. Here, we propose a combination of optical tools to manipulate single cells and measure the propagation of mechanical and biochemical signals inside them. Optical tweezers are used to trap microbeads that are used as handles to manipulate the cell plasma membrane; genetically encoded FRET-based force sensors inserted in F-actin and alpha-actinin are used to measure the propagation of mechanical signals to the cell cytoskeleton; while fluorescence microscopy with single molecule sensitivity can be used with a huge array of biochemical and genetic sensors. We describe the details of the setup implementation, the calibration of the basic components and preliminary characterization of actin and alpha-actinin FRET-based force sensors.

biophysics↗

bioRxiv2020

α-catenin regulates cell junction fluidity by cooperative mechanosensing

-catenin is a crucial protein at cell junctions that provides connection between the actin cytoskeleton and the cell membrane. At adherens junctions (AJs), -catenin forms heterodimers with {beta}-catenin that are believed to resist force on F-actin. Outside AJs, -catenin forms homodimers that directly connect the cell membrane to the actin cytoskeleton, but their mechanosensitive properties are inherently unknown. Surprisingly, by using ultra-fast laser tweezers we found that a single -{beta}-catenin heterodimer does not resist force but instead slips along F-actin in the direction of force. Conversely, the action of 5 to 10 -{beta}-catenin heterodimers together with force applied toward F-actin pointed end engaged a molecular switch in -catenin, which unfolded and strongly bound F-actin as a cooperative catch bond. Similarly, an -catenin homodimer formed an asymmetric catch bond with F-actin triggered by protein unfolding under force. Our data suggest that -catenin clustering together with intracellular tension engage a fluid-to-solid phase transition at the membrane-cytoskeleton interface.

biophysics↗