Kolade Adebowale
Immune cells use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices
Abstract:
Cell migration is essential to immune cell protection against disease. Circulating monocytes and T cells are recruited from blood, migrate through the collagen-stromal matrix to infiltrate the tumor. The tumor matrix not only stiffens during cancer progression, but in some cases exhibits enhanced viscous characteristics, resulting in viscoelastic behavior of the tissue. One consequence of viscoelasticity is time-dependent stress relaxation - a decrease in stress in response to applied deformation. However, the mechanisms by which viscoelasticity regulates migration are not fully understood.
To address this research gap, we developed interpenetrating networks (IPNs) of type-1 collagen and alginate, which enable independent tunability of stiffness and stress relaxation over physiologically relevant ranges for the three-dimensional culture of monocytes and T cells. We find that increased stiffness and faster stress relaxation independently enhanced the 3D migration of monocytes. Our mechanistic studies on monocyte migration indicate that WASP-mediated actin polymerization at the leading edge generates protrusive forces that generate a path to migrate in the confining viscoelastic matrices. Our ongoing work on T cell migration suggests that viscoelasticity regulates T cell migration via mechanosensitive ion channels.
Together, our data raise the possibility that changes in viscoelasticity could determine immune cell recruitment and ultimately shape the immune environment in tissue. Cell recruitment is an important consideration for the development of immune-targeted therapies where preferential recruitment of certain immune cell populations is desired. Our studies establish a platform to determine the role of mechanical cues in shaping the immune response and to leverage fundamental mechanisms to enable the rational design of “living drugs.”
Speaker: Kolade Adebowale, University of California, San Diego
Dr. Adebowale is currently an Assistant Professor in Bioengineering and a member of the Moores Cancer Center. He received his Ph.D. from Stanford University in 2021, where he studied the mechanobiology of cancer invasion. He then went on to complete his postdoctoral training in Cancer immunology in 2025 at Harvard University. Dr. Adebowale received the NSF GRFP, a Stanford Graduate Fellowship, an NIH F31 grant, and an NSF Ascend – MPS postdoctoral fellowship and was an NIH K99/R00 scholar. Dr. Adebowale’s research seeks to use experimental and computational approaches to integrate engineering design principles in cancer immunology to enable rational engineering and prediction of effective, next-generation immune cell therapies.
Host: Alexander Xu
Seminars start at 4:00 pm, and refreshments will be served at 3:45 pm. All seminars are held in the 2136 Physical Sciences Complex (#415) unless otherwise noted.