Real and Simulated Microgravity: Focus on Mammalian Extracellular Matrix

Abstract

The lack of gravitational loading is a pivotal risk factor during space flights. Biomedical studies indicate that because of the prolonged effect of microgravity, humans experience bone mass loss, muscle atrophy, cardiovascular insufficiency, and sensory motor coordination disorders. These findings demonstrate the essential role of gravity in human health quality. The physiological and pathophysiological mechanisms of an acute response to microgravity at various levels (molecular, cellular, tissue, and physiological) and subsequent adaptation are intensively studied. Under the permanent gravity of the Earth, multicellular organisms have developed a multi-component tissue mechanosensitive system which includes cellular (nucleo- and cytoskeleton) and extracellular (extracellular matrix, ECM) “mechanosensory” elements. These compartments are coordinated due to specialized integrin-based protein complexes, forming a distinctive mechanosensitive unit. Under the lack of continuous gravitational loading, this unit becomes a substrate for adaptation processes, acting as a gravisensitive unit. Since the space flight conditions limit large-scale research in space, simulation models on Earth are of particular importance for elucidating the mechanisms that provide a response to microgravity. This review describes current state of art concerning mammalian ECM as a gravisensitive unit component under real and simulated microgravity and discusses the directions of further research in this field.

Receptors Implicated in Microgravity-Induced Bone Loss

“…Glanzmann's Disease, which has a bone phenotype, is caused by specific mutations in Beta3 integrin [70]. As we will see in Section 5.1, the integrin signaling pathway has been implicated in low-gravity bone loss [58,[71][72][73][74][75][76][77]; however, the presence of these specific integrins, and others that use similar downstream signaling pathways in various cell types, and the multifarious effects microgravity has on humans, make it difficult to specifically identify the contributions of different cells and integrins to the loss of bone.…”

“…Changes in matrix protein expression could result in the altered physical support of cells and altered signaling to the cells. There are many examples of altered matrix protein expression in microgravity studies [72,73,207,208]. In bone, changes in acidic matrix proteins like osteocalcin and osteopontin could alter mineralization rates and quality due to their key role in the PILP process described earlier [110].…”

3D cell culture model: From ground experiment to microgravity study

“…Given that alterations in cell-to-cell interactions and interactions with the ECM are the main effects of microgravity on cells and may alter cell fate through these effects (Andreeva et al, 2022), hydrogelbased 3D cell models should be employed for microgravity studies to study the response of human tissues and organs to microgravity.…”

Gastric mast cell population in rats under ground-simulated weightlessness conditions and in early readaptation period

“…Так в работах авторов были показаны значимые изменения со стороны сердечно-сосудистой [10,15], иммунной [16,19], пищеварительной [1,3,12] систем, а также сенсомоторного и опорнодвигательного аппаратов [9,17]. Грависенситивность проявляется также на тканевом, клеточном и молекулярном уровнях [1,3,5,12,18]. Тучные клетки (ТК) являются повсеместно распространенными многофункциональными клетками соединительной ткани, активно вовлеченными в развитие как адаптивных, так и патологических процессов [1,8].…”