Cell Mechanics Innovations in Oncology: Harnessing Biophysical Principles for Cancer Intervention

In the first part of my talk, I will present our ongoing efforts to enhance T cell migration within tumors. While significant advances have been made in understanding the amoeboid-mesenchymal migratory balance, the mechanical processes by which T cells navigate tumor environments and the factors that determine their migration capabilities are still not well understood. To investigate this, we have developed a biophysical model of T cell migration that sheds light on the physical principles and molecular components modulating their movement [1]. Model predictions are supported by preliminary findings from in vitro studies on T cell migration.
In the second part of my talk, I will share our ongoing efforts to understand plasma membrane mechanics during leukemia cell cytokinesis. The actomyosin-based machinery that drives cell division is widely studied, but how actomyosin impacts the plasma membrane during cytokinesis is poorly understood. By using a combination of imaging and biophysical modeling, we found an extensive accumulation and folding of the plasma membrane at the cleavage furrow and the intercellular bridge [2]. Our work reveals that actomyosin-based mechanisms responsible for cytokinesis can also decrease membrane tension at the intercellular bridge, potentially supporting cytokinetic fidelity and locally affecting endocytosis, exocytosis, and cell signaling.
References
[1] R. Alonso-Matilla, P. P. Provenzano, D. J. Odde, “Biophysical modeling identifies an optimal hybrid amoeboid-mesenchymal phenotype for maximal T cell migration speeds”. bioRxiv, https://www.biorxiv.org/content/10.1101/2023.10.29.564655v3
[2] R. Alonso-Matilla, A. Lam, T. P. Miettinen, “Cell intrinsic mechanical regulation of plasma membrane accumulation in the cytokinetic furrow”. Proceedings of the National Academy of Sciences 121.29 (2024): e2320769121