Probing cellular microenvironments and tissue remodeling by atomic force microscopy

Ludwig T, Kirmse R, Poole K, Schwarz US.

Pflugers Arch. - Eur. J. Physiol. 2008 456:29-49

The function of cells is strongly determined by the properties of
their extracellular microenvironment. Biophysical parameters like
environmental stiffness and fiber orientation in the surrounding
matrix are important determinants of cell adhesion and
migration. Processes like tissue maintenance, wound repair, cancer
cell invasion, and morphogenesis depend critically on the ability of
cells to actively sense and remodel their surroundings. Pericellular
proteolytic activity and adaptation of migration tactics to the
environment are strategies to achieve this aim. Little is known about
the distinct regulatory mechanisms that are involved in these
processes. The system's critical biophysical and biochemical
determinants are well accessible by atomic force microscopy (AFM), a
unique tool for functional, nanoscale probing and morphometric,
high-resolution imaging of processes in live cells. This review
highlights common principles of tissue remodeling and focuses on
application examples of different AFM techniques, for example
elasticity mapping, the combination of AFM and fluorescence
microscopy, the morphometric imaging of proteolytic activity, and
force spectroscopy applications of single molecules or individual
cells. To achieve a more complete understanding of the processes
underlying the interaction of cells with their environments, the
combination of AFM force spectroscopy experiments with theoretical
modelling will be essential.