10/06/2026
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. research proposal defense by Prasan Malintha Wijayaweera, entitled “Investigating the Mechanical Response of Titin PEVK Motifs to pH and Calcium.”

Defense details

  • Date: Friday, Oct. 16, 2026
  • Time: 9 a.m.
  • Location: Olney Hall, Room 518

Committee

  • Advisor: Matthew J. Gage, Ph.D., Department of Chemistry, University of Massachusetts Lowell
  • Miklós Kellermayer, Ph.D., Department of Biophysics and Radiation Biology, Semmelweis University
  • Jin Xu, Ph.D., Department of Chemistry, University of Massachusetts Lowell
  • Jeffrey R. Moore, Ph.D., Department of Biological Sciences, University of Massachusetts Lowell

Abstract

The intrinsically disordered PEVK region of the giant sarcomeric protein titin contributes to titin-based passive elasticity in muscle. The PEVK contains repeating units of negatively charged Poly-E motifs and PPAK motifs. Although individual PEVK motifs have been studied at varying pH and calcium concentrations, their pH- and calcium-dependent mechanical behavior under force remains less studied. We used single-molecule magnetic tweezers to measure the force-extension behavior of individual PPAK, Poly-E and combined PPAK-Poly-E constructs under physiological and acidic pH conditions. According to our preliminary data, the three constructs showed distinct pH-dependent responses. The Poly-E motif exhibited greater extension at acidic pH than at physiological pH under the same force, while the PPAK motif showed a smaller change in the opposite direction. The combined PPAK-Poly-E construct showed greater extension at acidic pH, following the trend observed for Poly-E. We hypothesize that the negatively charged glutamate clusters of Poly-E function as major charge centers that contribute to the pH-dependent response and that PPAK modulates the overall mechanical response of the PEVK. We plan to further investigate these constructs by varying both pH and calcium ion concentration to determine how the electrostatic environment influences their mechanical behavior under force. Because we hypothesize that the glutamate clusters function as major charged centers, we plan to engineer more Poly-E constructs containing different numbers of glutamate clusters while maintaining a similar contour length. These studies will determine how local sequence features and electrostatic conditions regulate the force-dependent mechanical behavior of the PEVK region of titin.

All interested students and faculty members are invited to attend.