10/23/2026
By Amanda Vozzo

Matthew Gage, professor and chair of the Department of Chemistry at the University of Massachusetts Lowell, will give a talk on “The Role of pH in Conformational Dynamics of Intrinsically Disordered Proteins.”

Event Details

  • Date: Tuesday, Oct. 27, 2026
  • Time: 3:30 – 4:30 p.m.
  • Location: Olsen 503

Abstract

Biological systems adapt their mechanical properties to changing environmental conditions, allowing tissues to maintain function during periods of altered metabolic activity. Muscle is one example, where increased activity and anaerobic metabolism produce local pH shifts that can influence the structure and mechanics of sarcomeric proteins. We have been investigating how changes in pH regulate the giant muscle protein titin, including its intrinsically disordered PEVK region and immunoglobulin-like domains within the N2A region. Our previous work identified pH-dependent conformational changes in titin between pH 6 and 7, increased S100A1 binding under these conditions, and reduced passive myofibril stiffness as pH decreased. More recently, we have used poly-D and poly-E peptides as model acidic sequences to examine how charge, sequence composition, and protonation state influence titin interactions. In parallel, our studies of N2A immunoglobulin domains reveal that these structured regions are also sensitive to pH, suggesting that acidification can modulate titin through coordinated effects on both disordered and folded domains. Together, our results support a model in which metabolic acidosis promotes a more compliant titin state through pH-dependent changes in the PEVK and N2A regions and through altered interactions with acidic ligands and binding partners such as S100A1. This mechanism may allow titin-based passive stiffness to adapt dynamically to the history and intensity of muscle use.

Bio

Dr. Gage is professor and chair of chemistry at the University of Massachusetts Lowell. He received his BS in chemistry and a BS in molecular biology from the University of Wyoming and his doctorate in biochemistry and molecular biology from Purdue University, Indiana. His research focuses on understanding protein function at a molecular level. His group’s main focus is on the muscle protein titin and other proteins that interact with titin, and the group uses a range of biophysical and bioinformatics tools to try to understand the complex interplay among the various proteins in muscle. He has authored more than 30 peer-reviewed publications and has received funding from NIH, NSF and the Keck Foundation, among others, for his research.