Fluorescent Genetically Encoded Mechanosensors (fGEMs) for Measuring Cellular Tension and Screening Mechanotherapeutics

Inventor: Ben Sorum, Khalid Hanafy

Brief Description

This innovation introduces a genetically encoded fluorescent mechanosensor (fGEM) that reports changes in mechanical tension within living cells as changes in light intensity. By enabling direct visualization of cellular tension dynamics, this technology provides a powerful new approach for studying mechanobiology and for high-throughput screening of drugs that modulate cellular mechanics. The system bridges a major gap in translational medicine by linking mechanical dysfunction to disease mechanisms and therapeutic discovery.

Problem

Mechanical tension governs vital biological processes including cardiac contraction, vascular tone regulation, and neural activity. Dysregulated cellular tension contributes to diseases such as heart failure, hypertension, traumatic brain injury, and cancer. Despite its central importance, no current assay provides a direct, quantitative fluorescent readout of tension within cells. Existing methods—such as traction force microscopy or atomic force microscopy—are low throughput, technically demanding, and fail to capture real-time changes in intact cells. This lack of a simple, scalable, and real-time cellular tension assay represents a major unmet need in both research and drug discovery.

Solution

fGEMs are engineered fluorescent proteins that change brightness in response to mechanical forces. When expressed in cells, they emit measurable fluorescent signals proportional to the tension experienced by membranes or cytoskeletal structures. This innovation allows scientists and pharmaceutical companies to visualize tension in real time and rapidly identify drugs that either relieve or exacerbate cellular stress.

Technology

The fGEM system leverages circularly permuted fluorescent proteins integrated into mechanosensitive ion channels. Mechanical stimuli—such as membrane stretch, osmotic swelling, or cellular contraction—alter the protein’s conformation, resulting in a quantifiable change in fluorescence. The technology integrates cell biology, mechanobiology, and optical imaging to produce a mechano-fluorescent assay that can be deployed in diverse biological contexts, from cultured cells to tissue-level systems.

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