A Mechanoelastic Glimpse on Hyaluronan-Coated Extracellular Vesicles
Debashish Paul, A. Paul, Dipanjan Mukherjee, Saroj Saroj, Manorama Ghosal, Suchetan Pal, Dulal Senapati, J. Chakrabarti, Samir Kumar Pal, Tatini Rakshit
Abstract
Cancer cells secrete extracellular vesicles (EVs) covered with a carbohydrate polymer, hyaluronan (HA), linked to tumor malignancy. Herein, we have unravelled the contour lengths of HA on a single cancer cell-derived EV surface using single-molecule force spectroscopy (SMFS), which divulges the presence of low molecular weight HA (LMW-HA < 200 kDa). We also discovered that these LMW-HA-EVs are significantly more elastic than the normal cell-derived EVs. This intrinsic elasticity of cancer EVs could be directly allied to the LMW-HA abundance and associated labile water network on EV surface as revealed by correlative SMFS, hydration dynamics with fluorescence spectroscopy, and molecular dynamics simulations. This method emerges as a molecular biosensor of the cancer microenvironment.