Cells sense their microenvironments via adhesion sites, allowing them to attach to the extracellular matrix (ECM) and simultaneously acquire information about its mechanical properties. This information is further converted into biochemical signals affecting cell behaviors[1]. Mechanical properties of the tumor microenvironment and associated biochemical signaling are crucial to many steps of the metastatic cascade. Although, it is evident from past research that the mechanical properties of the microenvironment play an important role in tumor progression and metastasis, yet, it is still not clear if they also regulate the fate of disseminated metastatic cancer cells – their survival, dormancy, or reawakening. Disseminated cancer cells most often lead to metastatic relapses in patients and are responsible for a majority of cancer-related deaths, thereby becoming a critical therapeutic target[2]. The presented project aims to investigate the influence of biophysical properties of the environment on disseminated tumor cells. Previously, our group together with others developed a poly (hydroxyethyl methacrylate) (pHEMA) based polymer model system for mechanosensitivity studies with tunable contour lengths, allowing us to study the influence of molecular extensibility of polymer chains decoupled from any other biophysical cues, on cellular responses[3]. Presently, we are working on optimizing this system to get a higher throughput for cell biological experiments by self-assembly and photoimmobilization of carboxy terminated pHEMA block copolymers on polystyrene surfaces. Since integrin adhesions are instrumental in sensing matrix-associated mechanical signals, the immobilized polymers are then functionalized with RGD, a binding motif for integrins[1]. We will investigate if metastatic cancer cells could sense differences in molecular extensibility and respond with varied behaviors in terms of their adhesion, migration, and spreading. These analyses will be followed by investigating the potential influence of molecule extensibility on tumor cell cycling, proliferation, and finally dormancy. The results obtained will enhance our understanding of the role of biophysical cues on the fate of disseminated tumor cells and could be helpful in the development of new strategies to target them.

References

1. Amer, M., Shi, L. & Wolfenson, H. The 'Yin and Yang' of Cancer Cell Growth and Mechanosensing. Cancers 13, 2021. 

2. Montagner, M. & Dupont, S. Mechanical Forces as Determinants of Disseminated Metastatic Cell Fate. Cells 9, 2020. 

3. Gralla-Koser, R. Polymer Model System for Mechanosensitivity Studies: Decoupling Mechanics from Biological and Topographical Cues. Doctoral Thesis, Karlsruhe Institute of Technology, 2018.