Mechanobiology of hyaluronan-rich glycocalyx: How do giant polymers modulate cell adhesion.*

The overexpression of macromolecules in the cellular glycocalyx is strongly associated with cells in a pathological state, especially in cancer cell metastasis. More generally, hyaluronan-rich glycocalyx is upregulated during physiological processes that involve changes in adhesion or cell migration. In these scenarios, hyaluronan takes the form of giant megaDalton polymers that play a central physiochemical role in glycocalyx function. To examine the physical role of HA glycocalyx, we developed a biomimetic glycocalyx consisting of a microns-thick hyaluronan polymer brush. Our studies provide strong evidence that cells easily compress hyaluronan glycocalyx in order to establish molecular adhesions to the substrate. Further, we demonstrate that the compressed hyaluronan matrix modulates biophysical quantities such as the kinetics of cell adhesion, the topography of the cell membrane, and therefore, the tension on molecular adhesions. This work is instrumental in establishing a mechanistic view of how glycocalyx mediates cellular behavior.