Forces and elasticity in cell adhesion [Elektronische Ressource] / von Ulrich Schwarz

Sujets

• Biologie

Informations

• Publié par: universitat_potsdam
• Publié le: 01 janvier 2004
• Nombre de lectures: 24
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

Aus dem Max-Planck-Institut fur Kolloid- und Grenz achenforschung
Forces and elasticity in cell adhesion
Habilitationsschrift
zur Erlangung des akademischen Grades
Doktor rerum naturalium habilitatus
(Dr. rer. nat. habil.)
in der Wissenschaftsdisziplin Theoretische Physik
eingereicht an der
Mathematisch-Naturwissenschaftlichen Fakult at
der Universit at Potsdam
von
Dr. Ulrich Schwarz
geboren am 3.3.1966 in Stuttgart
Potsdam, im Januar 2004Contents
1 Introduction 1
1.1 General aspects of cell adhesion . . . . . . . . . . . . . . . . . 1
1.2 Cell-matrix adhesion . . . . . . . . . . . . . . . . . . . . . . . 7
1.3 Rolling adhesion . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.4 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2 Elastic substrates 15
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.2 Experimental method . . . . . . . . . . . . . . . . . . . . . . . 17
2.3 Computational method . . . . . . . . . . . . . . . . . . . . . . 18
2.4 Assumption of localized force and nite size e ects . . . . . . 22
2.5 Data simulation, regularization and resolution . . . . . . . . . 26
2.6 Analysis of experimental data . . . . . . . . . . . . . . . . . . 31
2.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
3 Bond dynamics 41
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
3.2 Single bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.3 Stochastic model for multiple bonds . . . . . . . . . . . . . . . 50
3.4 Two bonds under constant shared loading . . . . . . . . . . . 55
3.5 Cluster under constant shared loading . . . . . . . . . . . . . 58
3.6 linear shared loading . . . . . . . . . . . . . . . 65
3.7 Biological relevance . . . . . . . . . . . . . . . . . . . . . . . . 70
4 Elastic interactions 75
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4.2 Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.2.1 Force multipoles . . . . . . . . . . . . . . . . . . . . . . 794.2.2 Elastic interactions for physical dipoles . . . . . . . . . 80
4.2.3 in for active cells . . . . . . . . . . . . 82
4.2.4 Isotropic elastic medium . . . . . . . . . . . . . . . . . 85
4.2.5 External strain . . . . . . . . . . . . . . . . . . . . . . 86
4.2.6 Boundary-induced image strain . . . . . . . . . . . . . 87
4.2.7 Elastic interactions between cells . . . . . . . . . . . . 88
4.2.8 Summary modeling section . . . . . . . . . . . . . . . . 88
4.3 Examples of cell organization . . . . . . . . . . . . . . . . . . 90
4.3.1 Interaction with external strain . . . . . . . . . . . . . 90
4.3.2 Dipoles on elastic halfspace . . . . . . . . . . . . . . . 91
4.3.3 Dipoles in full space . . . . . . . . . . . . . . . . 94
4.3.4 Dipoles in elastic halfspace . . . . . . . . . . . . . . . . 96
4.3.5 Dipoles in sphere . . . . . . . . . . . . . . . . . 101
4.3.6 Summary example section . . . . . . . . . . . . . . . . 106
4.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Bibliography 111
Acknowledgements 128
Publications used in this work 129Chapter 1
Introduction
1.1 General aspects of cell adhesion
13The human body consists of around 10 cells, which can be classi ed into
more than 200 di erent cell types [2]. In order to function in the way we are
used to, the human body has to ful ll two seemingly contradicting princi-
ples. On the one hand, the cells in our body have to adhere to each other,
otherwise it would simply fall apart. On the other hand, they must be able
to reorganize quickly, for example when the body has to react to infection
or injury. Nature has evolved di erent strategies to cope with these con ict-
ing requirements. On the molecular level, biological adhesion is based on
relatively weak (non-covalent) interactions with short lifetimes of the order
of seconds. In order to achieve long-lived assemblies, the cells in our body
adhere through clusters of adhesions bonds, which prolongue lifetime both
by large bond numbers and by facilitating rebinding of single bonds. Be-
cause they are highly dynamic, biological adhesion clusters can react quickly
to new stimuli by association and dissociation. On the level of tissues, cells
build up an additional structure, the extracellular matrix (ECM), a network
of protein laments (e.g. collagen in the connective tissue) which provides
structural integrity to the tissue as a whole. The ECM is secreted by cells
during developement or after injury and is continuously remodeled by the
cells. It provides structural coupling between the cells without preventing
them from dynamic rearrangements.
Cells in a multicellular organism communicated with each other through
many di erent channels. The main mean of communication is release and
1CHAPTER 1. INTRODUCTION 2
capture of biochemical molecules [101]. In this way, cells can exchange very
speci c information. In solution, the biochemical information is supple-
mented by one additional degree of information, namely ligand concentration
(including di usion gradients). In cell adhesion, biochemical ligands are at-
tached to surfaces, like the plasma membrane of other cells or the proteins of
the ECM. Therefore now the biochemical information can be supplemented
by several additional degrees of information, including spatial distributions of
ligand which are not determined by di usion, and the mechanical properties
of the structure the cell attaches to. However, experimentally it is very di -
cult to quantify these additional factors. During recent years, rapid advances
in materials science have led to strongly improved control of extracellular lig-
and distribution and of the properties of the micromechanical environment.
As a result, the investigation of cellular response to the biochemical and phys-
ical properties of adhesive surfaces has become a very active area of research.
Apart from understanding the basic principles of cellular decision making in
a physiological environment, this eld is also driven by the prospect of de-
signing arti cial ents for cells, which on the one hand can function
as biomimetic environment, but on the other hand can also be more versatile
than biological ents, which result from speci c developmental pro-
cesses. In general, the combination of materials science and active biological
processes promises exciting new developments in the future [113]. In partic-
ular, judging from the developments of the last years, one might expect that
cell adhesion and materials science (including soft lithography, micro uidics,
and nanotechnology) are going to merge into a new eld in the future, which
also might lead to completely new biomedical applications, including new
kinds of biochips [129] and arti cial tissues [37].
Traditionally, cells have been studied on at substrates, like culture dishes
made from glass or plastic, which can be easily used in standard setups for
optical microscopy. In the early 1980s, Harris and coworkers introduced the
use of elastic substrates into cell biology [76, 75]. By crosslinking the surface
of silicon oil by exposure to heat, they created thin polymer lms which due
to their small thickness tend to buckle under cell traction. The resulting
wrinkles can be easily observed in optical microscopy and have been used
as qualitative assay for mechanical activity of cells since then. However, a
quantitative analysis of cell traction by elastic substrates has been achieved
only much later, mainly through the use of non-wrinkling elastic substrates
made from polyacrylamide (PAA). By inverting the elastic equations, it then
became feasible to calculate the details of cellular traction patterns from theCHAPTER 1. INTRODUCTION 3
Figure 1.1: The mechanical activity of cells can be monitored on elastic substrates.
Recent advances include the fabrication of micropatterned elastic substrates made
from the elastomer polydimethylsiloxane (PDMS). (a) A shallow pattern of dots
e ectively preserves the atness of the substrate, but can be used for easy visu-
alization of the deformations due to cell traction (small green arrows in inset).
Combined with uorescence markers for the sites of focal adhesion (white) and
linear elasticity theory, this allows to calculate the internal forces exerted at focal
adhesions (large red arrows) [6]. (b) When plated on a bed of exible microneedles
fabricated with PDMS, cellular traction generated in the actin cytoskeleton (red)
leads to displacement of the needle tips (blue). For small bending, the needles
act as linear springs, thus here force is simply proportional to displacement (cell
nucleus in green) [169].
displacement data (traction force spectroscopy) [40, 42]. Recent advances
in this eld include the use of micropatterned elastic substrates made from
polydimethylsiloxane (PDMS) [6, 169] and the combination of traction force
microscopy with uorescent constructs for cell-matrix contacts [6, 12]. A
growing body of evidence now suggests that the mechanical properties of
the extracellular environment (in particular its elasticity) play a much more
important role for cellular decision making than formerly appreciated. In
particular, it has been shown that cells more strongly upregulate cytoskeleton
and cell-matrix adhesion