Design Concept of Topographical and Mechanical Properties of Synthetic Extracellular Matrix to Control Cell Functions and Fates Through Actin Cytoskeletal Modulation - Innovative Approaches to Cell Biomechanics - page 168

11.3.1.4 Topography on the Scale of Ten to Hundreds of Nanometers:

Constraints on an Integrin Cluster

Topographical features ten to hundreds of nanometers work, as a direct constraint
on integrins, as illustrated in Fig. 11.5a . The size of the integrin cluster as a molecu-
lar clutch to transmit forces between ECM and the cytoplasm is characterized by
using an in vitro nanofabricated system (Schvartzman et al. 2011 ; Arnold et al.
2004 ; Lamers et al. 2010 ). As illustrated in Fig. 11.5b, c , a cluster consisting of
integrins spaced at 70 nm or less acts as a molecular link for transmission of a force
between ECM and the actin fi laments. The smallest number of integrin molecules
necessary to form the mechanical link is three (Coussen et al. 2002 ) or four
(Schvartzman et al. 2011 ). A spherical bead 40 nm in diameter allows for integrin
clustering with 3 or 4 integrin molecules (Felsenfeld et al. 1996 ). Such a unit can be
used as an element to specify the position and strength of a cytoplasm-ECM link
(Lamers et al. 2010 ).
Other representative elements are a nanodot, nanopit, and nanogroove (Bettinger
et al. 2009 ; Kim et al. 2012 ; Ventre et al. 2012 ). In cells on an array of these ele-
ments, the accessibility of a given region to the cell membrane is defi ned by the size
of features of the element, such as width and height/depth, and by spacing between
the elements. More than ~40 nm in height/depth and densely packed elements can
restrict integrin molecules only on the top of topographical elements (Lamers et al.
2010 ; Ventre et al. 2012 ).

a b c

Constrained
integrin cluster

FA activation FA inactivation

Increasing
spacing

Decreasing
feature size

Spacing

Feature size

< 8 nm < 70 nm

70 nm < Sp FS ∼ 100 nm FS Sp

Nanotopographical ECM

d

Unconstrained
integrin cluster

Actin filament

Myosin Focal adhesion, FA

Plasma Membrane

Integrin

Flat ECM

Fig. 11.5 Topography on the scale of ten to hundreds of nanometers as a constraint on an integrin
cluster. ( a ) Topography with feature size of ~100 nm effectively constrains integrins. ( b ) The adhe-
sive dots with 8 nm in diameter allow binding of one integrin per dot. Focal adhesion (FA) is acti-
vated and actin fi laments are linked to the adhesion spot when integrin molecules are spaced with
less than 70 nm. ( c ) FA is inactivated and actin fi laments are dispersed when integrin molecules are
spaced at 70 nm or more. ( d ) Formation of integrin clusters is unconstrained on a fl at ECM