Mechano-Regulation of Proteins at Low Forces: Paving the Way for Therapeutic Interventions

Mechanical forces play critical roles in the regulation of biological functions, including development, motility, and haemostasis. Aberrant mechano-regulation is implicated in human pathologies, including cancer and infarction. Proteins sense forces by undergoing conformational changes under external loads that trigger downstream signaling.

Despite its importance, mechanical regulation at the single-protein level remains poorly understood, in part due to a lack of suitable techniques to probe the physiological highly relevant low force (~1 pN) range.

ProForce aims to understand mechano-regulation at the single-molecule level in this previously inaccessible regime and to develop approaches to directly interfere with and correct aberrant force responses.

We propose to advance massively-parallel magnetic tweezers as the ideal tool for single-protein force measurements, as they can resolve very small forces (