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Chemical Engineering Seminar

Thursday, April 21, 2022
4:00pm to 5:00pm
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Spalding Laboratory 106 (Hartley Memorial Seminar Room)
Strategies for Engineering How Cells Sense and Interpret Mechanical Cues
John T. Ngo, Assistant Professor, Department of Biomedical Engineering, Boston University,

Cells can sense and interpret mechanical stimuli from their environment, but the ability to engineer customized mechanosensing capabilities has remained a synthetic biology challenge. Here, we introduce a set of synthetic Notch (SynNotch)-derived proteins that can be used to convert extracellular tensile forces into specifiable gene expression changes. By elevating the tension levels needed to induce SynNotch activation, in combination with structure-guided mutagenesis, we designed tunable mechanoreceptors with sensitivities in the physiologically relevant picoNewton (pN) range. Cells expressing these receptors could distinguish between varying levels of ligand-mediated tension and enact customizable transcriptional responses in turn. The utility of these tools was demonstrated by the design of a decision-making circuit, through which fibroblasts could be made to differentiate into myoblasts in response to mechanostimulation with tensile forces of distinct magnitudes. This work provides insight regarding how mechanically-induced structural alterations in proteins can be used to transduce physical forces into biochemical signals, and the system should facilitate further programming of force-related phenomena in biological systems.

For more information, please contact Sadie Rubalcava by phone at 6263953654 or by email at [email protected].