Microrheology of the pericellular matrix

Abstract

A membrane-coupled pericellular matrix (PCM) is expressed by a number of cell types and is in most cases associated with cell proliferation and migration. The PCM can be micrometers thick with the glycosaminoglycan hyaluronan (HA) as its backbone. For such an extended layer, however, the presence of hyaldherins like aggrecan or versican is a prerequisite. The latter, like HA, is associated with cancer progression and metastasis. As a model for a HA producing cell we used the human prostate adenocarcinoma cell line PC3. To probe the mechanical properties of the PCM we used microrheology, based on an optical trap equipped with far-field interferometry. We were able to probe the PCM at different distances from the membrane surface and found a soft (< 1 Pa) layer with a thickness of ∼ 1 μm in the absence of, and of ∼ 3 μm in the presence of exogenously added aggrecan. Furthermore, in the presence of aggrecan, part of the cells expressed long (<∼ 10 μm) microvilli extending from the surface. Probing in between the microvilli, we found again a soft (< 1 Pa) PCM. Both the viscoelastic PCM and the microvilli were absent on cells treated with the HA diminishing enzyme hyaluronidase, showing the structural importance of HA in the PCM.