how does a cell membrane repair itself

For example, lipid composition, distribution, and inter-lipid interactions actively control the rigidity and tension acting upon the plasma membrane, which in turn regulates cellular functions such as vesicle fusion, cell motility, and membrane resealing (Diz-Muoz, Fletcher, & Weiner, 2013; Gauthier, Fardin, Roca-Cusachs, & Sheetz, 2011; Togo, Krasieva, & Steinhardt, 2000). The .gov means its official. Houang EM, Sham YY, Bates FS, & Metzger JM (2018). Alterations in Phosphatidylcholine Metabolism of StretchInjured Cultured Rat Astrocytes. Rather than these roles being separated from each other, they overlap significantly such that one can easily be an extension of the other. Here the sugar (oligosaccharide) moiety faces the extracellular space interacting with other cells and extracellular ligands required for processes such as signaling, cell adhesion or intercellular interactions. Recombinant MG53 protein modulates therapeutic cell membrane repair in treatment of muscular dystrophy. As discussed above, sphingolipids in the plasma membrane are an important regulator of plasma membrane repair. Similar to PLC, phospholipase D (PLD) activity is also increased after injury and is required for repair (Arun et al., 2013). For an injury to a phospholipid bilayer alone (. Repeated eccentric exercise in healthy subjects (i.e., stepping down for 20 min) is known to induce damage so severe that muscle fibers degenerate over the following days and weeks (91, 131, 199). ESCRT machinery is required for plasma membrane repair. The membrane phosphoinositides, and PIP2 in particular, play an important role in regulating the interaction of F-actin with the plasma membrane (Kapus & Janmey, 2013; Saarikangas, Zhao, & Lappalainen, 2010). For example, the cytoskeletal proteins interact with membrane lipids to supply the cortical tension that regulates the global shape of the plasma membrane and produces cell movement (Cebecauer et al., 2018; Sezgin et al., 2017). Andrews NW, Almeida PE, & Corrotte M (2014). Bacterial pore-forming, What might membrane injury to muscle fibers look like? While membrane stabilization at the time of injury appears to improve membrane repair, a chronically rigid plasma membrane may inhibit the beneficial effects of transient lipid mobility after injury. Mechanistic principles underlying regulation of the actin cytoskeleton by phosphoinositides, Regulation of actin dynamics by PI (4, 5) P2 in cell migration and endocytosis, Pro-resolving lipid mediators are leads for resolution physiology. For example, shear force on the plasma membrane, such as that experienced during a mechanical injury, results in lipid mixing, which increases the mobility of signaling lipids and proteins residing in stable lipid microdomains (Petersen et al., 2016). Das S, Yin T, Yang Q, Zhang J, Wu YI, & Yu J (2015). This occurs primarily through the direct interaction of PIP2 with actin-binding proteins, and change in PIP2 distribution has been shown to precede actin build-up at the plasma membrane (Nebl, Oh, & Luna, 2000; Senju & Lappalainen, 2019; Tran, Masedunskas, Weigert, & Ten Hagen, 2015). Delivery of membrane (i.e. This is due to their lack of integration into the membrane under normal lipid packing conditions. To achieve these tasks, cells employ signaling networks, which respond to the changing microenvironment after injury and activate the diverse plasma membrane repair mechanisms with precise control in time and space. Lipids also react to the changing biochemical environment to become signaling molecules that determine the spatiotemporal dynamics of protein activation (Eyster, 2007) (Figure 1B). (C) Plasma membrane is dynamic and individual lipids have the capacity to move laterally within a leaflet (shown in pink) and between the leaflets (shown in blue). Because membrane tension limits the ability of cellular membranes to self-seal, cellular mechanisms that reduce membrane tension can promote membrane sealing. While PLC is able to cleave PC, the classic substrate of PLC is PIP2, which upon cleavage generates the membrane bound DAG and the cytosolic inositol trisphosphate (IP3) both of which are increased after injury (Lamb, Harper, McKinney, Rzigalinski, & Ellis, 1997; Vaughan et al., 2014). With an abundance of uncharged (zwitterionic) lipids and smaller amounts of neutral and anionic glycosphingolipids in the outer leaflet, and the negatively charged phosphatidylserine, phosphatidic acid and phosphatidylinositol within the inner leaflet, there exists a charge differential between the two plasma membrane leaflets (Steck & Lange, 2018; Zachowski, 1993). ASM activity at the plasma membrane has been shown to facilitate microvesicle shedding (Bianco et al., 2009). Endocytosis can also occur at sites of membrane invagination known as caveolae, and caveolae internalization has been implicated in membrane repair (Corrotte et al., 2013). GTPases are molecular switches that require the cycling of nucleotides to remain active. Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Drescher DG, Drescher MJ, Selvakumar D, Annam NP. increased lipid fluidity described in Section 3) and allows for the membrane associated PLD to diffuse outward from lipid rafts and interact with PIP2 in order to metabolize PC. See this image and copyright information in PMC. Lipid-soluble molecules and some small molecules can permeate the membrane, but the lipid bilayer effectively repels the many large . Copolymers such as poloxamer 188 avoid this potential issue by only stabilizing the plasma membrane once lipid packing density is sufficiently reduced, such as after an injury. The fluidity of the membrane is determined in part by its composition, with cholesterol and sphingolipid-rich regions being less fluid than those areas comprised primarily of phospholipids. Epub 2015 Oct 19. (2009). (2013). While PLD is also activated by calcium, recent findings have provided insight into the role of mechanical stress on initiating lipid signaling regulated by PLD (Petersen et al., 2016). In: StemBook [Internet]. However, uninjured muscle cells from Limb Girdle Muscular Dystrophy 2B (LGMD2B) patients show increased membrane fluidity, which is associated with their poor membrane repair ability (Sreetama et al., 2018). Thus, the signaling role of lipids affects membrane structure and how the wound is eventually resealed and remodeled, returning the plasma membrane to homeostasis. Repair of muscle fibers lacking the dysferlin protein, which results in reduced membrane stability, is improved by the presence of extracellular (oxidized) MG53 protein, suggesting that this protein can act on the outer leaflet of the plasma membrane to improve plasma membrane in diseased cells. PMC These remodeling events actively promote plasma membrane repair; however, they also act as extensions of the repair response and may continue long after successful resealing in order to restore the plasma membrane to its pre-injury state. Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly. Nojima H, Freeman CM, Gulbins E, & Lentsch AB (2015). To regulate the composition of plasma membrane lipids, cells utilize vesicle trafficking, which can add lipids (by exocytosis) or remove lipids (by endocytosis) from the plasma membrane. Additional structural changes the plasma membrane must adopt for repair include molding the shape of the membrane to limit wound expansion as well as pulling in the membrane edges to close the wound. The poor repair of these patient cells can be mirrored in healthy cells by increasing their membrane lipid mobility through the removal of cholesterol or by addition of a glucocorticoid (prednisone) (Heier et al., 2013; Sreetama et al., 2018). These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Bacterial pore-forming toxins oligomerize and insert in the plasma membrane of target cells forming a diffusible pore. Cell death occurs mainly by two methods: necrosis and apoptosis. In addition to allowing for the lateral translocation of membrane lipids, injury-triggered increase in membrane fluidity also results in reduced lipid packing. However, whether caveolae facilitate repair by buffering membrane tension remains unclear because, unlike the capacity of CLIC/GEEC endocytosis, caveolae make up a small portion (as small as 0.03%) of the membrane area and are not found ubiquitously in all cells (Gauthier et al., 2012; Sinha et al., 2011). Cell membrane disruption initially stimulates repair responses in the wounded cell itself, as described in this chapter, but other cells can subsequently respond to membrane disruption to "help" repair the membrane of the injured cell. Inherent plasticity and microfracture toughening mechanisms work together to prevent antlers from breaking. As a library, NLM provides access to scientific literature. In general, PIP2 is a positive regulator of F-actin polymerization and the presence of PIP2 increases the stability of the actin cytoskeletonplasma membrane interface. 2022 Aug 4;11:e80778. Disclaimer. Middel V, Zhou L, Takamiya M, Beil T, Shahid M, Roostalu U, Nienhaus GU (2016). While PC exists in both the inner and outer leaflet of the plasma membrane, the charged phospholipids PE, PI, and PS are almost exclusively maintained within the inner leaflet (Nicolson, 2014; van Meer, 1989). Int J Mol Sci. With larger injuries, the opposing force of membrane tension exceeds the resealing forces of lipid disorder at the edges of the disruption, negating the driving forces of spontaneous membrane resealing. The basement membrane of the basal cells attaches via hemidesmosomes to the underlying Bowman's layer, while anchoring fibrils pass through . Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion, Demonbreun AR, & McNally EM (2016). For example, venomous snakes store precursor molecules to instantly synthesize a suite of toxins via enzyme-mediated cascades. These cells cooperate with other specialized cells and become the building blocks of large multicellular . Endogenous mechanisms of repair in healthy cells appear to mimic the beneficial effect provided by poloxamer 188 by allowing for transient increases in lipid mobility while restricting fluidity increase to a relatively small spatial or temporal window. Alteration in this response inhibits the subsequent stages, tissue regeneration and remodeling, leading to increased tissue scarring. These same processes also work to dynamically control membrane fluidity by regulating the distribution of phospholipids, sphingolipids, and cholesterol in the membrane. Houang EM, Haman KJ, Filareto A, Perlingeiro RC, Bates FS, Lowe DA, & Metzger JM (2015). Zuzek A, Fan JD, Spaeth CS, & Bittner GD (2013). sharing sensitive information, make sure youre on a federal The tension forces acting on the plasma membrane are generally applied by three sources: the difference in hydrostatic pressure between the cell interior and extracellular space, the cortical cytoskeletal network, and the extracellular matrix to which the cell is attached (Gauthier, Masters, & Sheetz, 2012; Kozlov & Chernomordik, 2015) (Figure 2B). Why does our body heal itself? PIP2 dynamics after plasma membrane injury support a role for PIP2 in actin assembly during repair as its accumulation near the site of injury is generally delayed. FOIA In mammalian cells, lipids formed upon the phosphate and glycerol (e.g. Compared with cytosolic antioxidants, which can be detrimental to repair (Spaeth et al., 2012), vitamin E is membrane-localized and could therefore allow for the local buildup of oxidized lipids at the site of injury while preventing the global spread of lipid oxidation. Bethesda, MD 20894, Web Policies This relies upon the coordinated action of the machinery that polarizes the repair response to the site of injury, resulting in resealing of the damaged membrane and subsequent remodeling to return the injured plasma membrane to its pre-injury state.
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