Rising Star Faculty – Dr. Hari Parameswaran

Smooth muscle cells sense and respond to contractile stimuli as a collective

ABSTRACT:

Agonist-induced force generation by smooth muscle cells is currently understood in terms of an agonist molecule binding to a receptor on the cell surface, triggering a chain of intracellular signaling pathways that lead to force generation proportionate with the applied agonist dose. In this talk, I will demonstrate the existence of a communication system in human smooth muscle cells that uses mechanical forces to frequency modulate long-range calcium waves. An important consequence of this mechanical signaling is that changes in stiffness of the underlying extracellular matrix can interfere with the frequency modulation of Ca²⁺ waves, causing smooth muscle cells from healthy human donors to falsely perceive a much higher agonist dose than they actually received. This aberrant sensing of contractile agonist dose on stiffer matrices is completely absent in isolated smooth muscle cells, although the isolated cells can sense matrix rigidity. We show that the intercellular communication that enables this collective Ca²⁺ response in smooth muscle cells does not involve transport across gap junctions or extracellular diffusion of signaling molecules. Instead, our data support a collective model in which mechanical signaling among smooth muscle cells regulates their response to contractile agonists. Our findings suggest that pathological remodeling of the extracellular matrix can be a critical driver of disease progression in diseases like asthma. 

NARRATIVE BIOSKETCH:

Dr. Parameswaran is an Assistant Professor in the Department of Bioengineering at Northeastern University. His research focus includes mechanobiology of the smooth muscle, intercellular communication in multicellular ensembles, and methods for targeting extracellular matrix for asthma therapy. Dr. Parameswaran earned his Ph.D. in Biomedical Engineering from Boston University in 2009. His work is supported by awards from NIH and an early CAREER award from NSF.