Mechano-regulation via Cell Membrane-derived Nanovesicles to alter Collective Dynamics in Gliomas

Megha Jhunjhunwala^1*, Lin-Sheng Yu¹, Ping-Chen Kuo¹, Chi-Shuo Chen¹

¹Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

* Presenter:Megha Jhunjhunwala, email:megha.jhunjhunwala16@gmail.com

Mechanobiology is a cornerstone for several important biological phenomena. However, its role in biological applications remains undermined. Gliomas are one of the most challenging brain tumors with low therapeutic response. In this study, we focus on the mechano-biological application of cell membrane-derived vesicles (CMVs) or ‘cell shells’ and employ them as tactile cues for regulating collective glioma behavior. CMVs are currently used as nano drug-carriers, however, their impact on the mechano-response of glioma cells remains unknown. We observed that mechanical alteration of glioma collectives by application of glioma derived CMVs resulted in an increase in their traction stress proportional to the CMV:cell ratio, with the traction stress doubling for a tenfold increase in this ratio. In the presence of CMVs, the monolayers exhibited cell crowding behavior with their migration speed declining by nearly 40%. Furthermore, the presence of these glioma-derived CMVs improved drug diffusion in glioma spheroids via downregulation of mechano-signaling protein YAP-1, resulting in enhanced apoptotic events. Our novel application of CMVs to alter force distribution, cytoskeletal organization as well as physiological tendencies in tumor cells will open up new possibilities to tackle cancer metastasis and therapy resistance.

Keywords: Mechano-transduction, Glioma, Membrane Vesicles, Polarization, Collective Cell Migration