High-throughput mechanobiology: Force modulation of ensemble biochemical and cell-based assays

Abstract

Mechanobiology is focused on how the physical forces and mechanical properties of proteins, cells, and tissues contribute to physiology and disease. Although the response of proteins and cells to mechanical stimuli is critical for function, the tools to probe these activities are typically restricted to single-molecule manipulations. Here, we have developed a novel microplate reader assay to encompass mechanical measurements with ensemble biochemical and cellular assays, using a microplate lid modified with magnets. This configuration enables multiple static magnetic tweezers to function simultaneously across the microplate, thereby greatly increasing throughput. We demonstrate the broad applicability and versatility through in vitro and in cellulo approaches. Overall, our methodology allows, for the first time (to our knowledge), ensemble biochemical and cell-based assays to be performed under force in high-throughput format. This approach substantially increases the availability of mechanobiology measurements.