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The best example is “Cellular mechanics”. Mapping of cellular mechanical forces is important because it could help diagnose and treat diseases related to cellular mechanisms.For example, it is known that cancer cells do not move like normal cells, but it is not yet clear whether this difference is a cause or effect of the disease.Salaita explains that it is known "that if the EGFR is hyperactive, cancer can occur, and that one of the pathways for EGFR activation is through the uptake of ligands." Therefore, if it could be well understood how the mechanical forces of EGFRs play a role in the development of this disease, it would be possible to design drugs aimed at modifying this mechanical process and, consequently, stopping it”.
In recent years, several methods have been developed to study the mechanisms of cellular forces, but these have presented important limitations. In the case of one of them, genetic engineering, it is necessary to crack and modify cellular proteins, which leads to changes in the behavior of cells and, as a consequence, biased research results.In contrast, the technique developed by Emory University scientists is non-invasive and does not modify cells. In addition, for its application only a standard fluorescence microscope is needed, at both ends of which a chemically modified flexible polymer is placed.One end of the polymer carries an active fluorescence sensor that binds to a receptor on the cell surface. The other end is chemically anchored to the microscope stage.
When a mechanical force is produced in the cell, the polymer expands and the fluorescent signal of its sensor is activated, increasing its brightness. Measuring the amount of fluorescent light emitted allows knowing the amount of mechanical force exerted at the cellular level.
This new technique will make it possible to measure the mechanical forces of any individual protein or molecule on the cell surface, with greater spatial and temporal resolution than has been achieved until now, says Salaita. With it, many of the mysteries that cells pose to biology and chemistry could be unraveled: it could be known how cancer cells advance when a tumor expands, how these forces are involved in cell division and in the immune response, or the mechanisms that allow groups of cardiac cells to beat in unison could be understood.
According to Salaita: “our method could be applied to almost any (cellular) receptor, thus opening a path for the study of the mechanical and chemical interactions of thousands of receptors associated with cell membranes on the surfaces of practically any type of cell. . We hope that the measurement of cellular forces will become part of the standard repertoire of biochemical techniques used by scientists to study living systems." The results of this research have appeared in detail in the journal Nature Methods.
Mechanobiology is a new discipline, examining the properties of living organisms, from molecules to cells and tissues, which took off in the 2000s on theoretical bases born at the beginning of the 20th century. century at the borders of classical zoology, physics, and mechanics. This discipline is in full expansion, successively aggregating the skills and concepts of cell biologists, biophysicists and theoretical physicists, mechanics, mathematicians, and developmental biologists.
The term mechanobiology - to be differentiated from that of biomechanics usually used to designate the exploration of the mechanical properties of living organisms, their tissues or organs - brings together all the approaches aimed at highlighting and studying the fact that the majority of biological processes, at different scales ranging from molecules to organisms, are sensitive to mechanical stresses and deformations. The theoretical foundations of this discipline, which is revolutionizing biology, can be found in a treatise published by D'Arcy Thomson in 1917, "On growth and form“, postulating that morphogenesis can be explained by forces and movements – in other words by mechanics. Interestingly, D'Arcy Thomson published this hypothesis shortly after H. Wilson's publication founding the major role of intercellular adhesion in metazoan organization. It is evident that the establishment of mechanically strong physical contacts between cells greatly determines the propagation of mechanical stresses in the tissues.
One of the fields where the importance of this coupling between mechanics and chemistry is most visible is that of embryogenesis. Metazoan ontogeny is based on a succession of cell divisions from a single pluripotent cell, progressive differentiation of daughter cells under the control of epigenetic modifications controlling gene expression, and complex migrations of cells and cell groups, which, moreover, change shape. These migrations and shape changes result from the combination of traction and contraction forces generated within the cells themselves and mechanical stresses imposed by neighboring tissues and the extracellular matrix, the rigidity of which varies greatly with the stage of cell differentiation. Mechanical stresses propagate through tissues via intercellular junctions and the extracellular matrix. This mechanics driven by the forces generated by the molecular motors leads to large-scale tissue remodeling (tissue elongation during tissue convergence-extension processes), to coordinated cellular movements (epibolia, epithelial healing), to long-distance migrations (formation of the lateral line in fish), cellular constrictions (formation of the neural tube, dorsal closure of the embryo) and cellular extrusions and intercalations (during gastrulation) . These processes are strongly dependent on cell-cell and cell-matrix adhesion, and it is therefore not surprising that the main subcellular structures responsible for the attachment of cells to each other and to the matrix are anchored directly to the contractile network of actomyosin generating the pulling forces responsible for cell creep and shape changes. This proposition, known as the morpho regulatory hypothesis, shows all its fragility if we consider cellular adhesion outside the context of mechanical constraints, as was the case until the 1990s. However, it appears visionary if the cell adhesion is associated with the transmission of mechanical stresses. In this three-way game between gene expression/cellular adhesion/mechanical constraints, if the effect of the regulation of the expression of adhesion molecules on morphogenetic movements has long been established, the feedback effect of adhesion and mechanical stress on gene expression has long resisted analysis. Today, we can include the effect of mechanics on the epigenetic regulations responsible for the differentiation of somatic cells.
Biomechanics and mechanobiology lie on the same conceptual continuum and might differ at first glance only in the level of analysis, macroscopic/mesoscopic versus microscopic. Aristotle, the first, wrote about biomechanics in “De Motu Animalium”. Biomechanics applies well to the fields of organ physiology (functioning of the circulatory and respiratory systems, etc.), human or animal health (study of the physiological gesture solid mechanics to analyze motricity and locomotion. Biomechanics applies well to the fields of organ physiology (functioning of the circulatory and respiratory systems, etc.), human or animal health, human or animal health (study of the physiological gesture versus the pathological gesture), of the practice of sport. Conversely, biomechanics is not relevant to address essential pathophysiological processes involving mechanical constraints on organisms, tissues and cells, such as the adaptation of muscles and tendons to training, atrophy or regeneration. Obviously, biomechanics, as defined by these illustrious precursors, lacks essential ingredients to explain the impact of mechanical constraints on living organisms. Beyond the differences in scale, it is the consideration of these new ingredients, at the turn of the millennium, which is the basis of the shift from biomechanics to this new discipline that is mechanobiology. These essential properties of life, two in number, are located at the interface between physics and chemistry (or mechanics and biology) and stem from the particular nature of living matter. They can be formulated as follows: (1) the living organism, and in particular its basic unit which is the cell, is a non-equilibrium system consuming chemical energy to generate chemical work, but also mechanical work. In physical terms, it is an active material, i.e. it can generate forces by converting chemical energy - this is the case, for example, of those produced by molecular motors by hydrolysing ATPthese (active) forces, as well as the mechanical stresses (passive forces) imposed by the environment can be converted into a chemical or biochemical signal (change in conformation of a protein or of a protein network for example). These two mechanisms, mirrors of each other, constitute what is known as mechanotransduction pathways. By considering mechanotransduction, mechanobiology can now couple, within complex cycles, the mechanics of biological materials and their spatio-temporal responses of the biochemical type, to an imposed system of internal and external forces and constraints, and this from the scales molecular and cellular to tissues and organs.