PROBING CELLULAR ADHESION AT THE SINGLE-MOLECULE LEVEL - Life at the Nanoscale: Atomic Force Microscopy of Live Cells - page 222

adhesion complexes are continuously subjected to mechanical stresses. It
is thus important to study cell adhesion under applied force, which is the
most physiologically relevant scenario. The relatively recent development of
adequate tools to manipulate and apply forces at the nanoscale has allowed
us to probe receptor-ligand interactions one molecule at a time on living
cells. The present chapter will try to briely introduce the molecular players
involved in cell adhesion and to describe the particular application of the
atomic force microscope (AFM) to study the behaviour of these peculiar
proteins under force.
The principal actor in cellular adhesion is the CAM. There is a wide
variety of CAMs that have different functions depending on the type and state
of the cell, and the biophysical and biochemical microenvironment in which
they exist. Figure 11.1 shows the four major families of CAMs.

are
transmembrane multidomain glycoproteins that mediate heterotypic cell-cell
adhesion. Selectins bind speciic carbohydrate structures through calcium-
dependent interactions via their lectin domains. The cytoplasmic domains
can be linked to the actin cytoskeleton. 1,2 Members of the

Selectins

immunoglobulin

superfamily (IgSF) are multidomain proteins that mediate homo- and

heterotypic cell-cell adhesion. Members of the IgSF can present a varying
number of the Ig fold, a compact and rigid structure with one or more disulide
bonds, from which one or more are binding domains. These molecules are
present in cells from the nervous system, the vascular endothelium and blood
cells and are commonly involved in cell recognition. Some members of the
IgSF are linked to the actin cytoskeleton via other proteins, e.g. ezrin. Both
homo- and heterotypic interactions of some IgSF members have been probed
with AFM. are transmembrane multidomain glycoproteins that

primarily mediate calcium-dependent homotypic cell-cell adhesion. The
ive repeats can interact with any of the repeats of an opposing cadherin,
leading to multiple possibilities of cadherin-cadherin interaction. Speciicity
of tissues is in great part mediated by cadherins. Structural stability is
accomplished through the formation of structures such as desmosomes and
adherens junction, in which cadherins can link to intermediate ilaments
and the actin cytoskeleton, respectively. The adhesion strength of various
types of cadherins has been studied at both multiple and single-molecule
levels on puriied proteins and on living cells. 7-9

4-6

Cadherins

are heterodimers
and mediate both cell-cell and cell-extracellular matrix heterotypic binding.
Integrins are composed of an α and a β chain, containing a large extracellular
domain, a single membrane spanning region and a short cytoplasmic domain.
Humans have 19 α and 8 β integrin subunits that combine to form more than

Integrins