The energetics of rapid cellular mechanotransduction

Cells throughout the human body detect mechanical forces. While it is known that the rapid (millisecond) detection of mechanical forces is mediated by force-gated ion channels, a detailed quantitative understanding of cells as sensors of mechanical energy is still lacking. Here, we combine atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells expressing the force-gated ion channels (FGICs) Piezo1, Piezo2, TREK1, and TRAAK. We find that, depending on the ion channel expressed, cells can function either as proportional or nonlinear transducers of mechanical energy and detect mechanical energies as little as similar to 100 fJ, with a resolution of up to similar to 1 fJ. These specific energetic values depend on cell size, channel density, and cytoskeletal architecture. We also make the surprising discovery that cells can transduce forces either nearly instantaneously (<1 ms) or with a substantial time delay (similar to 10 ms). Using a chimeric experimental approach and simulations, we show how such delays can emerge from channel-intrinsic properties and the slow diffusion of tension in the membrane. Overall, our experiments reveal the capabilities and limits of cellular mechanosensing and provide insights into molecular mechanisms that different cell types may employ to specialize for their distinct physiological roles.

Automated summary

This study combines atomic force microscopy with patch-clamp electrophysiology to determine the physical limits of cells as sensors of mechanical energy. The researchers find that cells can function as proportional or nonlinear transducers of mechanical energy and detect very small mechanical energies with high resolution. They also discover that cells can transduce forces either nearly instantaneously or with a substantial time delay. The study provides insights into the capabilities and limits of cellular mechanosensing and the molecular mechanisms involved.