Table Of ContentMechanobiology of the
Endothelium
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Mechanobiology of the
Endothelium
Editor
Helim Aranda-Espinoza
Fischell Department of Bioengineering
University of Maryland
College Park, MD
USA
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A SCIENCE PUBLISHERS BOOK
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Preface
The endothelium is responsible for regulating the exchange of material from
the blood to tissues and organs. It is exposed to shear stress from the blood
stream as well as pressure from tissues and smooth muscle cells. It is also
exposed to different mechano-chemical environments, such as blood and
extracellular matrix. It is quite an incredible task for this cell monolayer
to maintain homeostasis. Therefore, endothelial cells are remarkable
mechanotranducers. They need to convert chemical signals into mechanical
outputs on a daily basis, as well as the reverse: translate the mechanical
forces they feel into biological and chemical signals to adapt or respond
accordingly. The most evident example of such a response is the remodeling
of the endothelial cell cytoskeleton in response to shear stresses from the
blood fl ow. Because of these types of responses, the endothelium has been
the subject of intense research from biological, biochemistry, biophysical,
and mathematical perspectives. However, the combination of these fi elds,
with the emergence of mechanobiology as a scientifi c discipline, has opened
the possibility of studying the endothelium with a broader perspective.
Mechanobiology is a relatively new scientifi c discipline. It merges
mechanics and biology to study systems where forces elicit a biological
response or a biological function is subjected to specifi c forces. When
the response or the forces in the biological system change, a pathological
condition can ensue, as in atherosclerosis. Therefore, studying the
mechanobiology of these biological systems offers the opportunity to
obtain a fundamental understanding and the possibility to translate this
understanding into disease diagnosis and/or treatments.
The endothelium is an excellent example of where the study of
mechanobiology is already being put to use. For instance, aspects of
mechanobiology have been used in the design of heart valves and studying
the endothelium of the valves. Mechanobiology has also been applied to
the study of angiogenesis and the forces that affect the mechanobiology of
the endothelium. Many facets of mechanobiology of the endothelium are
reviewed in this book, including the examples cited above. Other highlights
of the book include: studies toward understanding the scientifi c basis of
the endothelial cells as mechanosensors, using the endothelium as a means
vi Mechanobiology of the Endothelium
to deliver drugs to specifi c tissues, studies on the role of endothelium
biomechanics in cancer metastasis and atherosclerosis, and research on
understanding cell transmigration. Because of space constraints, some
specifi c areas have been left out, but I hope that this book still manages to
cover important topics for readers that are starting to delve into the study
of endothelium mechanobiology and for experienced researchers that need
an overview of the topics covered here.
The team of authors consists of experts in their respective fi elds and the
work devoted to each chapter is greatly appreciated. The editor has learned
a lot on each subject and it is expected that the reader will learn as much.
Each chapter is independent of one another and therefore they can be read
individually and not necessarily in sequence. Please enjoy!
August 2014 Helim Aranda-Espinoza
Contents
Preface v
1. The Endothelium as a Mechanosensor 1
Rachel E. Neubrander and Brian P. Helmke
2. Mechanobiology of the Endothelial Nucleus 23
Elizabeth A. Booth-Gauthier, Stephen Spagnol and Kris Noel Dahl
3. Cancer Metastasis and Biomechanics of the Endothelium 47
Claudia T. Mierke
4. Valvular Endothelial Mechanobiology 80
Suthan Srigunapalan and Craig A. Simmons
5. Environmental Factors that Infl uence the Response of the 103
Endothelium to Flow
Tracy M. Cheung and George A. Truskey
6. Differential Response of the Endothelium to 132
Simultaneous Chemical and Mechanical Stimulation
in Infl ammation Response
Ryan B. Huang and Omolola Eniola-Adefeso
7. The Role of Cholesterol and Lipoproteins in Control of 146
Endothelial Biomechanics
Irena Levitan, Tzu-Pin Shentu, Mingzhai Sun and Gabor Forgacs
8. Implications of Fluid Shear Stress in Capillary Sprouting 166
during Adult Microvascular Network Remodeling
Walter L. Murfee
9. Endothelial Cell Adhesion Molecules and Drug Delivery 185
Applications
Daniel Serrano and Silvia Muro
viii Mechanobiology of the Endothelium
10. Leukocyte Transendothelial Migration: A Biophysical Event 227
Kimberly M. Stroka
Index 251
Color Plate Section 255
CHAPTER
1
The Endothelium as a
Mechanosensor
Rachel E. Neubrander1 and Brian P. Helmke1,2,3,*
The endothelium is the single layer of cells that lines blood and lymph
vessels and the heart. Because of its location at these interfaces between
tissue and blood or lymph, the endothelium serves several important
physiological functions that maintain tissue homeostasis. Most importantly,
the endothelium provides a barrier that regulates transport of fluid,
macromolecules, proteins, and cells into and out of tissues. Second, the
endothelium is a key player in autoregulation of tissue perfusion in response
to changes in blood pressure, potentiating blood fl ow rate through vessels
by controlling their diameters. In normal circumstances, the endothelium
also prevents blood clotting.
Both transport barrier and autoregulation functions involve complex
interactions between biochemical signaling in endothelial cells and the
local biophysical environment in the blood vessel wall. For example,
the blood-brain barrier (BBB) that separates blood from cerebrospinal
fl uid consists of endothelial cells with tight junctions that limit transport
to small macromolecules. Tight junctions, which consist of a complex
1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
2Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville,
VA 22908.
3NanoSTAR Institute, University of Virginia, Charlottesville, VA 22908.
*Corresponding author: [email protected]
