Table Of ContentFundamentals and
Biotechnological Applications
edited
Louisiana State University
Baton Rouge, Louisiana
Joseph Roos
Ethyl Corporation
Richmond, Virginia
MarceD l ekker, Inc. NewY orkB . asel Hong Kong
Library of Congress Cataloging-in-Publication Data
Cell adhesion : fundamentals and biotechnological applications /
edited by Martin Hjortso, Joseph W. Roos.
p.c m. - (Bioprocesst echnology ; v.2 0)
Includes bibliographical references and index.
ISBN 0-8247-8945-8
1.C ella dhesion.2 .B ioreactors.3 .B iotechnology.
I. Hjortso, Martin 11. Roos, Joseph W.
111. Series.
TP248.25.C42C149 59 4
660’.63-d~20 94-22882
CIP
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Series Introduction
Bioprocess technology encompasses all of the basic and applied sciences as
well as the engineering required to fully exploit living systems and bring
their products to the marketplace. The technology that develops is eventu-
ally expressed in various methodologies and types of equipment and instru-
ments built up along a bioprocess stream. Typically in commercial produc-
tion, thes tream begins at theb ioreactor, which can bea classical fermentor,
a cell culture perfusion system, or ane nzyme bioreactor. Then comes sepa-
ration of the product from the living systems and/or their components
followed by an appropriate number of purification steps. The stream ends
with bioproduct finishing, formulation, andp ackaging. A given bioprocess
stream may have some tributaries or outlets and may be overlaid with a
variety of monitoring devices and control systems. As with any stream, it
will both shape and be shaped with time. Documenting the evolutionary
shaping of bioprocess technology ist he purpose of this series.
Now that several products from recombinant DNA and cell fusion tech-
niques are on the market, the new era of bioprocess technology is well
established and validated. Books of this series represent developments in
various segments of bioprocessing that have paralleled progress in the life
sciences. For obvious proprietary reasons, some developments in industry,
although validated, may be published only later, if at all. Therefore, our
continuing series will follow the growth of this field as it is available from
both academia and industry.
W. Courtney McGregor
This Page Intentionally Left Blank
Preface
Over the past several years, cell adhesion has progressedf rom a phenome-
non of peripheral interest to biochemical engineerst o become a useful tool
in bioreactor design and bioseparations. Along with thesei nnovations have
arisen increased demands for better understanding of the phenomena that
underlie cell adhesion. The aim of this book is to present the student or
researcher in biochemical engineering with an introduction to the basic
phenomena that govern cell adhesion and top rovide descriptions of bioen-
gineering processes in which cell adhesion plays an important part.
Cell adhesion hasa lready been studied extensively because ofi ts medical
significance. The ability of different cells to adhere or aggregate plays a
crucial role in suchp rocesses as microbial infections, spread ofc ancer
through the body, and plaque formation on teeth. However, the abundant
literature thath as come out of the biomedical research isn ot always partic-
ularly useful to the biochemical engineer, since the medical perspective is
much different from the engineering point of view. Engineering applica-
tions of cell adhesiona re presented int he research literature, butt o date no
comprehensive reference work has been available on this topic. In view of
this, it appeared timely to assemble a book dedicated to the engineering
aspects of cella dhesion.
To theb iochemical engineer, cell adhesion ias potential problem as well
Preface
as a valuable tool. Cell adhesion may lead to biofouling of process equip-
ment but is purposely employed in immobilized bioreactors to influence
reactor performance. In the case of anchorage-dependent animal cells, ad-
hesion to a solid support is essential for cultivation. Cell-cella dhesion
or flocculation may be undesirable during a fermentation but is often an
important step in the final separatioonf cells and broth. In all cases, judi-
cious engineering practice requires an understanding of cell adhesion and
the controlling physical and chemical factors.
In putting together this book, we had two objectives: to detail the funda-
mental aspects of cell adhesion and to present contemporary engineering
aspects of cell adhesion.
Cell adhesion mechanisms can bgee nerally classified as two types, occur-
ring via either specific or nonspecific interactions, both of which are ideal-
ized descriptions of the adhesion process. On a fundamental level, all types
of adhesion are mediated by the same forces, van der Waals and electro-
static forces between molecules on the cell surface and molecules on the
adhesion surface. However, the distribution of these forces is perceived
differently in the two cases. In nonspecific adhesion, the adhesion forces
are viewed as being continuously distributed over the contact area,m aking
it possible to describe the strength of the adhesion in terms of an adhesive
energy, the free energy reduction per area of contact. In specific adhesion,
on the other hand, the forces are concentrated into discrete bonds between
receptors on the cell surface and complementary ligands on the adhesion
surface. Bonds are formed only when the shapes of the two molecules
match each other in such a way that groups on the two molecules can
approach one another closely enough for van der Waals and electrostatic
forces to become effective. It is the steric hindrance that prevents formation
of bonds between noncomplementaryl igands and receptors that give rise to
the specificity of this type of adhesion. The two introductory chapters
emphasize the characteristics of specific adhesion. Limited discussion is
directed toward nonspecific adhesion and generally addresses situations
where it can be viewed as a limiting case of specific adhesion. In general, it
is felt that aspects of nonspecific adhesion can bed ealt with more appropri-
ately in light of particular applications that exploit the phenomena. Discus-
sions of these applications, where appropriate, are included in the remain-
ing chapters.
The second half of the book is application-oriented. In a series of chap-
ters, leading researchers discuss cell adhesion as applied to problems of
interest to biochemical engineers. Cell adhesioni s discussedi n several chap-
ters as a tool forb ioreactor design. The use of biofilm formation inb ioreac-
tors is discussed for three separate cell types: microbial, animal, and plant
cells. Each type of reactor has different characteristics dictated by the re-
Preface i
quirements of the adhering cells. In another chapter, cell-cell adhesion or
flocculation is discussed. Flocculation, a procedure that has been used for
centuries as a method to isolate biomass from broth,i ncreases cell sedimen-
tation rates. Recently, flocculation has found many new applications in
the manipulation of bioprocesses. While both cell aggregation and biofilm
formation can result from anyc ell adhesion mechanism,i ndividual applica-
tions cell adhesion may require careful preparation of the adhesion sur-
face. This is the topic of the last chapter, in which different supports and
their chemical modification are discussed.
It would be satisfying if the processes described in the application chap-
ters could be modeled in terms fundamental events and kinetics. How-
ever, cell adhesion models based on fundamental processes have not yet
reached a stage where this is altogether possible. Consequently, engineering
models of processes involving cell adhesion often use concepts and a no-
menclature specific to the area. although a common nomenclature is
used in the introductory chapters, we have not attempted to keep this no-
menclature through thea pplication chapters.
Martin A. Hjortso
Joseph W. Roos
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Contents
Series Introduction W. Courtney McGregor iii
Preface V
Contributors xi
1. Kinetics of Ligand-Receptor Bond Formation 1
Joseph W. Roos and Martin A. Hjortso
2. Mathematical Modelso f Specific Cell Adhesion Phenomena 35
Martin A. Hjortso and Joseph W. Roos
3. Cell Adhesion in AnimalC ell Culture: Physiological and
Fluid-Mechanical Implications 61
Manfred R. Koller and Eleftherios T. Papoutsakis
4. Surface Immobilizationo f Plant Cells 111
Jean Archambault
5. Cell Aggregation and Sedimentation 135
Robert H. Davis
6. Microbial Biofilms and Biofilm Reactors 187
Brent M. Peyton and William G. Characklis
Description:Offers a detailed introduction to the fundamental phenomena that govern cell adhesion and describes bioengineering processes that employ cell adhesion, focusing on both biochemical and biomedical applications. All industrially relevant issues of cell adhesion - from basic concepts, quantitative expe
