Paper Number
PO6
Session
Poster Session
Title
Using bi-disperse microrheology to measure human mesenchymal stem cell remodeling of hydrogels on multiple length scales
Presentation Date and Time
October 13, 2021 (Wednesday) 6:30
Track / Room
Poster Session / Ballroom 1-2-3-4
Authors
- McGlynn, John A. (Lehigh University, Department of Chemical and Biomolecular Engineering)
- Schultz, Kelly M. (Lehigh University, Chemical and Biomolecular Engineering)
Author and Affiliation Lines
John A. McGlynn and Kelly M. Schultz
Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015
Speaker / Presenter
McGlynn, John A.
Keywords
experimental methods; biological materials; gels
Text of Abstract
Hydrogels can improve wound healing by delivering additional cells to aide in the healing process. Human mesenchymal stem cells (hMSCs) are commonly delivered due to their role in coordinating healing. For hydrogels to deliver hMSCs, they must enable migration out of the gel and into the wound. This requires understanding how hMSCs modify rheology across length scales. hMSCs break cross-links using matrix metalloproteinases (MMPs), migrate several microns and eventually degrade the bulk hydrogel. How each scale is remodeled must be considered when designing a scaffold. To measure length scale dependent remodeling and correlate rheology with motility, we use bi-disperse multiple particle tracking microrheology (MPT). Bi-disperse MPT measures Brownian motion of two different sized particles simultaneously to quantify length scale dependent structure and rheology. We encapsulate hMSCs in a poly(ethylene glycol)-based hydrogel that is degraded when cross-links are cleaved by MMPs. We measure three length scales: 0.5 and 2.0 and 4.5 μm. We measure that the 2.0 μm length scale is more remodeled than the 0.5 μm length scale. We identify cytoskeletal tension (CST) as the source of differences in remodeling by inhibiting it and measuring similar remodeling on each scale. We then quantify how hMSCs apply force by measuring if particles have directed motion, measuring that 2.0 μm particles are directed towards specific regions in the field of view while 0.5 μm particles are undirected. Regions where 2.0 μm particles are directed are where force is applied by CST. We measure that 2.0 and 4.5 μm scales are remodeled more than the 0.5 μm scale for the same cellular speed. These results indicate that larger particles are trapped in a partially degraded gel which is pulled by the cell while 0.5 μm particles diffuse through the network. This work measures remodeling across length scales and can improve material design to direct hMSCs to wounds using length scale dependent structure.