Introduction
The success of tissue engineering is dependent on the ability to promote the desired cellular processes. Given the intricate process involved in tissue development and regeneration, it is crucial to understand how microenvironment regulates cell behavior. Generally, mechanical signals contribute significantly to the development of human beings, especially during embryonic growth, where they influence cell activities such as contraction and protrusion.
Here, both internal and external factors influence cell interactions, thus fostering the process of shaping up cells in the body. Other stimuli to cell activity in developmental processes include physical factors such as mechanical or osmotic stress (Janmey & Miller, 2010). Generally, mechanical forces are just as effective as chemical forces in the development of an individual from embryo stage to old age, mainly due to their role in controlling cell division and alignment of body plan and organs through cytoskeletal forces, shear, and ECM elasticity tensions.
The effect of mechanical signals on development processes may be observed from their role in the regulation of transcription. This is done through mechanical forces such as hydrostatic pressure, shear stress, compressive force, tensional stress, cell traction force, and cell prestress (Mammoto, Mammoto, & Ingber, 2012).
This paper will discuss the role of mechanical signals in regulating developmental processes. In addition, the paper will highlight several control effects of mechanical forces on various cell activities, including early embryonic development, tissue morphogenesis, and organ formation. This is in addition to a discussion on mechanical signal transduction on cell-extracellular Matrix adhesions, cell-cell adhesions, and cell shape distortions. Moreover, the paper will provide a comparison of mechanical signals and chemical signals in influencing cell proliferation and tissue development.
Mechanical Signals control of Cell-Extracellular Matrix Adhesions
The extra-cellular matrix is the living environment for stem cells; it comprises of proteins and carbohydrates that bind cells together. In addition, it supports and surrounds cells, regulating the cell activities, and providing structure for cell movement. In addition, the natural living environment comprises of four niche components, which dictate the ultimate fate and functions; these include soluble factors, direct cell-cell contact, extra-cellular matrices, and forces. Understanding the influence of biomechanical factors on the fate of stem cells will eventually help the development of synthetic approaches that may trigger stem cells to differentiate into desirable phenotypes (Chelluri, 2012).
From the time of fertilization, through embryonic development to the maturation of an organism, mechanical signals play a crucial role in the formation of body organs, systems, and processes; the exposure of cells to various stimuli enhances the production of forces that influence development. Moreover, cell interaction during the developmental process facilitated by mechanical forces or signals tends to be an important aspect that goes as far as enhancing endurance and resistance of body organs to various infections or diseases such as osteoporosis.
For example, changes in microenvironment such as the osmotic pressure that result in mechanical signals interaction with cell activity may “significantly alter the structure of ECM proteins and the activity of soluble growth factors and cytokines” (Mammoto, Mammoto, & Ingber, 2013).
Although mechanical signals are known to influence cell activity, there are instances where cell activity responds to changes that occur when cytoskeletal forces combine with other mechanical forces, causing a state of differentiation. For instance, the activity of the actin cytoskeleton in mechanical transduction always plays a significant role in the developmental process. Moreover, cellular mechanosensitivity plays a central role in the viability and function of cells in the development, maintenance, and pathology of tissues.
In addition, mechanosensitivity allows mechanical signals to induce an active reorganization of the cell cytoskeleton and readjustment of the contractile forces exerted by the cell (Mammoto, Mammoto, & Ingber, 2012).
During development, signals sent by mechanical forces influence cell protrusion and contraction, thus affecting cell growth patterns, especially during embryo development; this tends to influence the size and rate of growth of the embryo. Moreover, gene transfer from the host or parent takes place at this stage, with certain responses tending to be installed in cells when interactions take place.
These gradients partially limit the expression of target differentiation genes and produce distinct organ-specific cells. These allow maturation of tissue and organs in the embryo-generating process. Nevertheless, mechanical forces not only have a role in developmental processes but also are crucial in maintaining the function of most adult organs and organ systems; these include the heart, blood vessels, lungs, and hematopoietic system (Mammoto, Mammoto, & Ingber, 2012).
Stem cell differentiation plays a critical role in organism development or in the wound healing process. Here, external cell activities promote the development of extra-cellular forces that tend to interact with adjacent tissue cells that are infected. However, due to resistance from external tissue boundaries, the extra-cellular matrix plays a vital role in the expansion of cell walls to replace the worn-out tissues in the wound. However, when these restrictions are more complex and not corrected through mechanical forces activity, there are chances of unregulated tissue growth occurring. Nevertheless, “inappropriate development of compressive pressure can lead to ectopic cartilage formation” (Janmey & Miller, 2010).
Mechanical Signals Control of Cell-Cell Adhesions
Mechanical signals can regulate cell behavior through either extrinsic mechanical forces or intrinsic matrix stiffness. In addition, fluid shear stresses in the blood vessels can directly influence endothelial cell gene expression and biosynthetic activities, which in turn regulate the blood vessel remodeling process. It is also worth noting that fluid shear and hydrostatic compression in bone tissue facilitate bone cell mechanical adaptation and tissue remodeling. Mechanical forces in the development process work throughout the development process in embryogenesis. Importantly, spring forces are generated when a spring is compressed or stretched and then acts by trying to force a return to its natural length.
During fertilization, sperm cells are forced in the ovum cell by mechanical forces generated by the activity of the actin bundle and the osmotic pressure in the uterus, thus interfering with the cell membrane and activating the mechanosensitive ions reaction process. Here, the shape of the cells is altered in order to enhance fertilization to take place and form new cells that degenerate to an embryo. The liquid-form surface tension that results from the embryonic formation process is then exposed to external stimuli that influence further cell activity to improve tissue growth through extra-cellular matrix authentication.
The surface tension is determined by differences in intercellular adhesion and cytoskeletal prestress governed by cadherins and actomyosin based contractility. Moreover, “tensional forces, traction and prestress cell shape stability requires the establishment of a mechanical force balance within the cytoskeleton” (Janmey & Miller, 2010). Such a balancing effect allows the cytoskeleton to instinctively steady cell shape as well as to regulate the process of cell determination. On the other hand, shear stress that emanates from the circulation system propagates cell activity in the endothelial, thus hastening the process of cell determination.
It is worth noting that mechanical forces associated with cell strain rise externally from imposed mechanical stimuli common during force transmission to cells through the ECM. It is important to note that mechanical stress may be generated by the interaction of cell activity forces with external stimuli; in other circumstances, “coordination with outside–in stimuli, anchored cells also probe their microenvironment to sense and respond to the stiffness of the microenvironment by pulling on the ECM” (Provenzano & Keely, 2011).
During this process, the ECM adhesions actively participate in enhancing cell activity, especially where the transfer of forces from the external stimuli to the cell generation process is concerned. Moreover, intracellular forces tend to create channels for the transmission of stimuli forces in order to enhance cell activity and enhance the effectiveness of mechanical signals in the development process. For instance, “myosin-based contractility has a role in regulating stem cell differentiation, epithelial morphogenesis, branching morphogenesis of epithelial and endothelial cells, and the cancer-associated invasive phenotype that is induced in mammary epithelial cells by stiff 3D matrices” (Provenzano & Keely, 2011).
Generally, when cells interact, they generate a functional force that influences their contraction and protrusion, leading to adhesions that transfer force to the ECM and thus enhancing growth and development in an organism. In a situation where the microenvironment stimuli and cells tend to function at a stable condition, there is likely to be calmness in cell activity, unlike in a situation where tensional forces are high, thus precipitating abnormal cell proliferation or behavior.
Importantly, proliferation affects the regulation of cell activity; the epidermal growth factor and insulin-like growth factor are receptors known to promote cell proliferation. The mechanical signals transmitted through the structural component provide the cytoskeleton with signaling events to regulate cell proliferation (Mammoto, Mammoto, & Ingber, 2012).
It is important to understand the process of cytoskeletal remodeling and its influence on cell behavior, especially during cell proliferation resulting from mechanical forces stimulation. This would enhance understanding of the influence of mechanical signals on gene transfer and installation during cell proliferation; the understanding will enhance the establishment of the reason why organisms behave in certain ways when compared to their parents.
The mechanical signals provide a complex feedback loop between cell proliferation and pathways that regulate intracellular contraction to produce force through the cytoskeleton, thus regulating FA signaling. An example of mechanical forces is the impact on cell behavior from studies on cell distortion or cell shape as an independent variable. Cell deformation was a result of the tractional forces attached to the ECM substrate that cells exert on their own adhesions.
Experiments on cell deformation show how surrounding cells form adhesion forces on the cellular surface, thus creating extreme tension. Due to the existing soluble factors, the amounts of saturated soluble mitogens create an island that regulates different factors, thus making them constant. This fluid enhances the transmission of stimuli or circulation process in order to influence vascular organs’ functionality, especially in grown-up organisms or human beings.
In addition, vascular remodeling enhances better transport of nutrients and other morphogenic factors. In this mechanical process, fluid shear stress is critical; here, erythroblasts play an important role in the development process. Research on mechanical forces in cell proliferation has established their role in helping the provision of regenerating cells, especially in cancer research. In cancer patients, the regenerating cancer cells are stopped through cell degeneration procedures such as radiation control (Chelluri, 2012). Moreover, researchers in the field of medicine have provided ways of cell proliferation that have enhanced cancer medication in recent years.
Mechanical forces generated in the cytoskeleton of living cells play a central role in the control of tissue development during the early and last stages of embryogenesis. Changes in the cellular force help in balancing the integrin signaling pathways and produces global changes in cytoskeletal structure that are central to this process. The local environment may be altered by changing the level of cell biochemical remodeling or the number of cells packed within a tissue volume restricted by a rigid ECM. Cells tend to sense these local changes in the mechanical cues and integrate them with other chemical and adhesive signals in their microenvironment (Chelluri, 2012).
For cells to switch locally between different stable phenotypes, multiple genes or other regulatory elements must simultaneously alter their activity. Mechanical forces, therefore, play an important role in morphogenesis and tissue patterning, and these physical cues are important chemical factors for developmental controls throughout all stages of embryogenesis. External forces have been known to influence the process of embryo formation, especially when mechanical forces interfere with the process of cellular proliferation to the extent of promoting changes in cell shape and size.
The process cytoskeleton tension is the driving force behind many of these mechanical processes and mechanochemical transduction events. This is evidenced by the tendency of cells responding to the coupling effect of mechanical signals and chemical stresses. Here, it is worth noting that as much as cell-generated tensile forces modify chemical signals transmitted by cells, they also tend to deform the surrounding cells thus creating significant changes in signaling process.
Generally, mechanical and chemical signals tend to be interdependent such that it would be impossible for cells to respond effectively to one form of signal in absence of the other, although mechanical signals are more active and influential. Indeed, the differences between these two forms of signal do not necessarily affect cell proliferation, as they tend to share a number of intracellular molecules and processes that contribute significantly to cell activity.
One of the differences between the two signals is that, while chemical signals decay rapidly in strength as distance from the source increases because they are carried in fluids and gases, mechanical signals are long lasting in terms of strength because they do not need to be pushed along by fluid or air, but they are transferred along networks of fibers in an electronic-like form. In addition, mechanical signals are wide in scope in relation to their capability, as they can handle complex information unlike chemical signals, which tend to be restricted to only less complicated chemical gradients.
New methods, including mechanosensing and mechanotransduction, collaborate with chemical stimuli to control cell and tissue function. In addition, disruption of normal mechanical environment can perturb cell function. There are instances when cell activities may be altered or changed by rigidity of their stimuli despite chemical environment remaining intact, thus resulting to tissue abnormality or emergence of disease. It is generally normal for tissues to be controlled by elastic properties, thus there arises a challenge when they encounter a stiff stimuli, thus interfering with cell formation and proliferation. This abnormal cell activity may result to malignant growth and uncoordinated body processes, thus contributing to emergence of diseases such as cancer and cardiac problems.
Mechanical signals play a vital role in regulating cell activity in embryo development. Here, mechanical forces control asymmetric and symmetric cell division by regulating the activities of cytoskeletal microtubules and contractile actin microfilaments, which polymerize in order to modulate spindle positioning (Mammoto, Mammoto, & Ingber, 2013). In addition mechanical forces influence tissue Morphogenesis is through a process called coupling, where cell-generated mechanical forces combine with chemical forces to regulate the size of epithelia cells, especially during gastrulation.
Here, Cytoskeletal contractile forces constrict the apical surfaces, thus creating pull and push forces that close the dorsal epidermal opening in gastrulation. Moreover, it has been observed that, during gastrulation and neurulation, mechanical forces play a significant role in enhancing the elongation of body axis by controlling cell protrusive and contractile activities (Mammoto, Mammoto, & Ingber, 2013).
The body plan and profile is also a product of mechanical forces, which contribute significantly to the development of the whole body system and its functional components; for instance, during the latter stages of embryonic development, mechanical forces help in aligning and assembling vital organs such as lungs and blood vessels, as well as body systems such as circulation and hematopoetic system.
These forces work in tandem with chemical forces, especially in functionality and development of lungs through amniotic fluid flow and movement. It is also important to note that there is likelihood of mechanical stresses appearing during development processes; however, this is usually resisted through muscle tensions that strengthen inter-cell junctions, thus contributing to tissue growth and maturation (Mammoto, Mammoto, & Ingber, 2013).
Conclusion
In conclusion, the importance of mechanical processes in regulating development in tissues and cells is well defined in this essay. Proper mechanical environment is required for extensive and well-organized functions of the cell organism. Generally, cell functions and forces associated with mechanical forces are enough to help understand the role of mechanical signals in developmental processes. Cell differentiation, proliferation, and degeneration have helped body organs and chemical composition of the body to be well organized. Nevertheless, major cell functions are required to ensure that the body functions in the right way.
All in all, mechanical signals influence tissue formation and development in organism; however, their role in body systems such as the circulation, cardiovascular, and excretion needs to be researched further in order to establish their application and mitigation capability in related problems. Mechanical processes in the cell development help in enhancing functions of major organs in the body.
The body requires these cell functions to enhance flow of blood to different parts and organs. In the lungs, cells in charge of infusing blood with oxygen work in mechanical environment that enhances oxygenation of the body. Nevertheless, it is important to note that, mechanical processes are central in enhancement and improvement of bodily functions in many organisms and they play an integral role in embryo development.
Indeed, factors of regulating mechanical processes are mostly functional. Nevertheless, a combined approach of physical techniques and other disciplines related to cell and tissue development is need in advancing research on developmental processes. This would also help in establishing cell formation and development patterns, especially in modern disease diagnostic processes for cell-related diseases such as cancer and tumors.
References
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Mammoto, A., Mammoto, T., & Ingber, D. (2012). Mechanosensitive Mechanisms in Transcriptional Regulation. Journal of Cell Science, 125(13), 3061-3073.
Mammoto, A., Mammoto, T., & Ingber, D. (2013). Mechanobiology and Developmental Control. Annual Review of Cell Development Biology, 29(1), 27-61
Provenzano, P., & Keely, P. (2011). Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling. Journal of Cell Science, 124(1), 1195-1205.