Lekka / Navajas / Radmacher | Biomedical Applications | E-Book | sack.de
E-Book

E-Book, Englisch, 370 Seiten

Reihe: De Gruyter STEM

Lekka / Navajas / Radmacher Biomedical Applications

Biomedical Aspects of the Mechanical Properties of Cells and Tissues
1. Auflage 2023
ISBN: 978-3-11-098943-4
Verlag: De Gruyter
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

Biomedical Aspects of the Mechanical Properties of Cells and Tissues

E-Book, Englisch, 370 Seiten

Reihe: De Gruyter STEM

ISBN: 978-3-11-098943-4
Verlag: De Gruyter
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)



This book is dedicated to the discussion of several biomedical applications of the mechanical phenotyping of cells and tissues to specific disease models. The topical chapters on mechanics in disease are preceded by chapters describing cell and tissue structure and their relationship with the biomechanical properties, as well as by the description of dedicated sample preparation methods for the nano- and microscale mechanical measurements.

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Zielgruppe


Graduate students in Physics, Medicine, Life Sciences; researcher

Weitere Infos & Material


Cell and Tissue Structure


4.1 Cell Structure: An Overview


Malgorzata Lekka
Institute of Nuclear Physics, Polish Academy of Sciences, Kraków, Poland

In living organisms, molecules subject to all the physical laws form spatial complex (bio)chemical structures capable of extracting energy from their environment and using it to build and maintain their internal structure. Each component of a living organism has specific functions at organ and cell levels that maintain cells in a steady state of internal physical and chemical conditions (homeostasis). Diseases occur due to many reasons. Some of them are linked with spontaneous alterations in the ability of a cell to proliferate, while others result from changes generated by external stimuli from the cell microenvironment. Regardless of the cause of diseases, cellular homeostasis undergoes severe alterations to which cells must adapt to survive. Otherwise, they can die. Recent studies on the role of biomechanics in maintaining cells and tissue homeostasis in various pathologies show that it is extremely important to link physical and chemical phenomena with the alterations in the structure of living cells or tissue. Accordingly, in this chapter, basic structural elements are described.

A cell is an individual unit containing various organelles used to maintain all living functions (Lodish et al., 2004). An example of the simplest cell is a bacterium. In bacteria, all cellular processes are carried out within a single cell body. In multicellular organisms, different kinds of cells perform different functions. Cells embedded within their microenvironment (the extracellular matrix, or ECM) assemble in highly specialized tissues (connective, muscle, nervous, and epithelial) as the basis for organ formation. Despite the high level of cellular specialization, most of the animal cells possess similar cellular structures (Figure 4.1.1).

Figure 4.1.1: Schematic structure of an animal cell.

A major component of the cell is the nucleus. The nucleus is a highly specialized organelle that contains genetic information encoded in DNA strands. It is surrounded by a double-layer phospholipidic membrane (called the nuclear envelope) that separates it from other regions present inside the cells. The nuclear membrane contains holes (called nuclear pores) that regulate the passage of molecules to and from the nucleus. A semifluid matrix found inside the nucleus is called nucleoplasm. Within it, most of the nuclear material consists of chromatin, the less condensed form of the cell’s DNA that organizes to form chromosomes during mitosis or cell division. The nucleus also contains one or more nucleoli, which are membraneless organelles that manufacture ribosomes – the cell’s protein-producing structures.

Close to the cell nucleus, an endoplasmic reticulum with associated ribosomes is located. This organelle is responsible for protein and lipid synthesis. Newly synthesized proteins and lipids are sorted in the Golgi apparatus, from which they are distributed to other cellular compartments or membranes.

The mitochondria are organelles where energy is stored. They contain two major membranes: the outer and the inner membranes. The inner membrane has restricted permeability, and it is loaded with proteins involved in electron transport and ATP (adenosine triphosphate) synthesis, used for energy production. The outer membrane has many protein-based pores that enable the transport of ions and small molecules.

The lysosomes are specialized organelles that function as the digestive system inside cells and are responsible for the degradation of material taken in from outside the cell and for the digestion of obsolete cellular components. Lysosomes contain arrays of enzymes capable of breaking down any type of biological polymers – proteins, nucleic acids, carbohydrates, and lipids.

Within the cellular space, multiple types of various vesicles (e.g., endosomes) are required for the molecular transport within the cell and between the cell and its environment.

Each cell is surrounded by a cell membrane that separates the cell interior from the surrounding microenvironment. It is not only a structural scaffold within which cells are embedded but also contains various proteins, proteoglycans, and other molecules that participate in distinct cellular functions like adhesion or migration. The cell membrane consists of a double layer of phospholipids in which proteins are embedded. The interaction of the cell with the ECM mainly happens through the action of integral (going across the cell membrane) and peripheral (attached to the outer side of the cell membrane) proteins regulating the transport of substances to and from the cell.

All intracellular organelles are embedded in the cytoplasm filling the cell interior. The cytoplasm contains two elements, that is, the cytosol (a liquid fraction) and the cytoskeleton (a network of protein filaments).

The cytosol is the intracellular fluid comprised of water, dissolved ions, large water-soluble molecules, smaller molecules, and proteins. Within it, multiple levels of organization can be found. These include concentration gradients of small molecules such as calcium, large complexes of enzymes that act together to carry out metabolic pathways, and protein complexes such as proteasomes that enclose and separate parts of the cytosol.

The cytoskeleton is a mesh-like structure composed of various filamentous proteins. Apart from its structural functions related to maintaining cellular shape and providing the tool for organelles’ arrangements, the cytoskeleton participates in various processes through interactions with other proteins, such as muscle contraction, cell division, migration, adhesion, and intracellular transport. The cytoskeleton helps establish regularity within the cytoplasm and, together with the plasma membrane, determines the mechanical stability of the cell. The cytoskeleton comprises three main elements – actin, intermediate filaments, and microtubules. A mesh-like structure composed of actin filaments is located beneath the cell membrane. Intermediate filaments form a ring around the cell nucleus and span over the whole cell volume. Microtubules have one end located at the microtubule-organizing center (a centrosome) close to the cell nucleus and the other in the cell membrane.

In the following chapters, detailed descriptions of cell structural components are presented.

Reference


Lodish, H., A. Berk, P. Matsudaira, C. A. Kaiser, M. Krieger, M. P. Scott, L. Zipursky and J. Darnell (2004). “Molecular Cell Biology.” ?

4.2 The Cytoskeleton


Wolfgang H. Goldmann
Biophysics Group, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Physics, Germany

Acknowledgment: The author thanks Ms. Ceila Marshall (MA) for proofreading the manuscript.

Adherent cells are anchored via focal adhesions to the extracellular matrix, which is essential for force transduction, cell spreading, and migration. Focal adhesions consist of clusters of transmembrane adhesion proteins of the integrin family and numerous intracellular proteins, including talin and vinculin. They link integrins to actin filaments and are key players of focal adhesions that build up a strong physical connection for transmitting forces between the cytoskeleton and the extracellular matrix. These proteins consist of a globular head and a tail domain that undergo conformational changes from a closed, autoinhibited conformation in the cytoplasm to an open, active conformation in focal adhesions, which is regulated by phosphorylation.

4.2.1 Actin Cytoskeleton


Over the years, much research has provided information on the cellular function of the cytoskeleton, which has helped in understanding the many aspects of cell behavior. Components of the cytoskeletal network are major regulators of processes as diverse as establishing and maintaining gross cell morphology, polarity, transduction of force, motility, and adhesion to matrix components and cells. The cytoskeleton has long been proposed to be involved in the organization/reorganization of reporters in the plasma membrane. It is, therefore, critical to cell recognition mechanisms for many types of associations. These can range from tissue formation to the immune killing of foreign cells. Hence, the association of cytoskeletal elements with membrane components became a paradigm for signal transduction to the cytoplasm from the cell surface and vice versa....


__Malgorzata Lekka holds a PhD in physics with a specialization in medical physics. She studied physics at the Jagiellonian University (Kraków, Poland), completed in 1993. In 1993, she started to work at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN, Kraków, Poland), where she obtained the PhD in 1998 in physics (specialization: biophysics) with the thesis focused on the elasticity of cancerous cells measured by atomic force microscopy (AFM), followed by habilitation in 2008. Since 2016, she is a full professor at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN, Kraków, Poland. From 2016, she headed the Department of Biophysical Microstructures at the IFJ PAN (https://www.ifj.edu.pl/oddzialy/no5/nz55). She has published over 140 papers in international peer-reviewed journals (H-index 32, researcher identifiers: A-3706-2016 (WoS), 0000-0003-0844-8662 (Orcid), and 7003401456 (Scopus)).

__Daniel Navajas, University Barcelona, Spain.

__Alessandro Podestà (AP) holds a PhD in Materials Science and since 2015 he is associate professor at the Department of Physics "Aldo Pontremoli" of the University of Milano, Italy. AP has published about 100 papers on international peer-reviewed journals (H-index 30, complete bibliographic record with metrics at: https://www.webofscience.com/wos/author/rid/E-6568-2010; ORCID: https://orcid.org/0000-0002-4169-6679). In 2012 AP obtained the National Academic Qualification (ASN) to apply for Full Professor positions in Experimental Physics of Matter (02/B1).

Since 1999, AP is active in the field of characterization of physical and chemical properties of systems and interfaces at the nanoscale by Atomic Force Microscopy (AFM) techniques. AP leads the AFM group of the Interdisciplinary Centre for Nanostructured Materials and Interfaces (CIMaINa) of Università degli Studi di Milano. The research activity of the AFM laboratory developed over the years under the guidance of AP since its foundation in 1999, along two parallel but strongly interconnected tracks: the development of experimental techniques and protocols based on atomic force microscopy, and the application of such protocols to the study of nanostructured systems and interfaces. The synergistic combination of research and development activities related to atomic force microscopy has always characterized the scientific approach of AP within the Physics Department and CIMAINA @UNIMI; this expertise has been enhanced at European and international level in funded research projects and in commissioned research activities.

__Manfred Radmacher, University Bremen, Germany.



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