Two-way traffic on the road to plasma membrane repair. Blauch LR, Gai Y, Khor JW, Sood P, Marshall WF, Tang SKY. The spatial arrangement of lipids at the plasma membrane is not only important for GTPase recruitment, but also for their activity. The lipids in the membrane control the function of the membrane - keeping some products inside and some outside. doi: 10.7554/eLife.80778. Gauthier NC, Fardin MA, Roca-Cusachs P, & Sheetz MP (2011). Epub 2008 Oct 9. This phenomenon may be explained by the kinetic energy imparted on the membrane lipids by mechanical disruption, which can result in lipid mixing without relying on membrane tension (Petersen, Chung, Nayebosadri, & Hansen, 2016). Inflammatory exudates provide insights into the regulation of the first stage of wound repair inflammation.
Lysosome - Genome.gov The basement membrane of the basal cells attaches via hemidesmosomes to the underlying Bowman's layer, while anchoring fibrils pass through . Tran DT, Masedunskas A, Weigert R, & Ten Hagen KG (2015). Mechanical feedback between membrane tension and dynamics. Instead, distinct inter- and intra-leaflet heterogeneity exists. Collectively, these changes enable lipids to initiate/regulate local signaling allowing precise spatial and temporal control over downstream plasma membrane repair pathways. Gurtner GC, Werner S, Barrandon Y, & Longaker MT (2008). PMC Self-repairing cells: How single cells heal membrane ruptures and restore lost structures Many organisms and tissues display the ability to heal and regenerate as needed for normal physiology and as a result of pathogenesis. As a library, NLM provides access to scientific literature. Alkaloid molecules protect plants from bacterial infections. The radiation could prevent the DNA from replicating correctly. Another broad group of lipid carriers that are recognized for their role in activating stem cells are extracellular vesicles (EVs), which are released locally at the site of injury or from a distant site and through their lipid and other cargoes regulate regeneration of injured tissues by way of stem cell activation (Riazifar, Pone, Ltvall, & Zhao, 2017). During regeneration, sphingolipids such as sphingosine 1-phosphate (S1P) are known for their growth promoting effect on tissue resident stem cells (Calise et al., 2012; Nojima, Freeman, Gulbins, & Lentsch, 2015). All of the above mechanisms for regulating the physical properties of the membrane play important roles in determining how a cell responds to plasma membrane injury and undergoes successful repair. Following this, accumulation of Annexin 4 and Annexin 6 results in folding and inward contraction of the injured membrane, respectively (Boye et al., 2017). 8600 Rockville Pike and transmitted securely. Trends Cell Biol. The plasma membrane is semi-permeable, allowing the cell to communicate with and utilize resources from its surrounding environment. Roach AN, Wang Z, Wu P, Zhang F, Chan RB, Yonekubo Y, Du G (2012). These observations suggest that lipids are not bystanders during the repair process, but are instead actively involved in organizing the playing field on which repair machinery operates. The radiation could damage the cell's DNA, but the DNA repairs itself. Sphingomyelin also confers different properties to the plasma membrane than the phospholipids, not least due to its preferential association with sterols (Ramstedt & Slotte, 2006). Andrews NW, Almeida PE, & Corrotte M (2014). These membrane invaginations require the presence of caveolin proteins, loss of which can result in poor membrane repair and muscular dystrophy (Gazzerro, Sotgia, Bruno, Lisanti, & Minetti, 2010; Minetti et al., 1998). Here we will discuss the current knowledge of how lipids facilitate plasma membrane repair by regulating membrane structure and signaling to coordinate the repair response, and will briefly note how lipid involvement extends beyond plasma membrane repair to the tissue repair response. These cells cooperate with other specialized cells and become the building blocks of large multicellular . Presence of PS at the free membrane wound edge helps directs the annexin proteins to this site in a calcium-dependent manner, where they perform vital functions required for stabilization and shaping of the repairing membrane (see Section 3.3). Front Cell Dev Biol. Gazzerro E, Sotgia F, Bruno C, Lisanti MP, & Minetti C (2010). The physical properties of the plasma membrane are governed in large part by the effect of lipid interactions at the population level. government site. These phospholipids are important for the formation of other molecules that are involved in cell signaling and help to bind proteins and carbohydrates to the outer cell membrane. Caveolae internalization repairs wounded cells and muscle fibers, Regulation of endocytosis, exocytosis, and shape by membrane tension, Paper presented at the Cold Spring Harbor symposia on quantitative biology. This is called apoptosis. This process is itself facilitated by mechanisms that regulate membrane tension, in particular the re-establishment of the actin cortex. Potez S, Luginbhl M, Monastyrskaya K, Hostettler A, Draeger A, & Babiychuk EB (2011). Idone V, Tam C, Goss JW, Toomre D, Pypaert M, Andrews NW.
Plasma Membrane (Cell Membrane) - Genome.gov This lipid binds ALIX and is capable of budding vesicles away from the cytosol (Matsuo et al., 2004). Cholesterol and various proteins are also embedded within the . Disclaimer. Cheng JP, Mendoza-Topaz C, Howard G, Chadwick J, Shvets E, Cowburn AS, Nichols BJ (2015). This involves a series of distinct, but mutually dependent stages including inflammation, regeneration, and remodeling of the tissue (Gurtner, Werner, Barrandon, & Longaker, 2008). Quantification of membrane tension after injury to fibroblasts demonstrated that a minimum tension force was reached by approximately 30 seconds post-injury, but tension was fully restored by 80 seconds post-injury (Togo et al., 2000). Before Epub 2008 Mar 3. Furthermore, ASM activity at the injury site would locally produce ceramide from sphingomyelin. The membrane patch may serve only temporarily as a surface barrier replacement that is subsequently remodeled and removed via exocytic and/or endocytic machinery. Amongst other causes, this can be due to physical, chemical, infectious, biological, nutritional or immunological factors. VBP15, a novel antiinflammatory and membranestabilizer, improves muscular dystrophy without side effects, Cellular mechanisms and signals that coordinate plasma membrane repair. Therefore, injury-triggered protein-lipid interactions that result in modified lipids generates signaling that allows for changes in activity and localization of plasma membrane repair machinery. One model explaining membrane injury in dystrophin-deficient muscle fibers proposes that an initial injury causes a local influx of calcium and a local region of hypercontraction. Sheng R, Chen Y, Gee HY, Stec E, Melowic HR, Blatner NR, Fujiwara TK (2012). SM utilizes the ceramide (Cer) backbone and can be used to generate the signaling lipid sphingosine-1-phosphate (S1P). Every cell has a fatty membrane that self-assembles when placed in water, then reassembles when a breach occurs. This dissociation has the effect of allowing Rho GTPase translocation to the membrane where it can interact with signaling lipids.
Membrane Damage - an overview | ScienceDirect Topics Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. This cytoskeletal assembly is regulated by Rho GTPase activity, which triggers F-actin accumulation at the site of injury. In this way, lipids play an important role in polarizing the cellular response to an injury. Modular, cascade-like transcriptional program of regeneration in, R01 GM113602/GM/NIGMS NIH HHS/United States. 2017 Jul 11;114(28):7283-7288. doi: 10.1073/pnas.1705059114. Senju Y, Kalimeri M, Koskela EV, Somerharju P, Zhao H, Vattulainen I, & Lappalainen P (2017). . The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. Cell wounding activates phospholipase D in primary mouse keratinocytes. 2015 Sep;45:2-9. doi: 10.1016/j.semcdb.2015.09.023. This study showed that endocytosis occurs after membrane resealing and is mediated by the CLIC/GEEC pathway effector GRAF1, which is implicated in repair of muscle fiber plasma membrane injury (Lenhart et al., 2015). Among these lipids, PC is the most abundant in the plasma membrane and is formed by adding choline to the DAG backbone. Plasma membrane repair in health and disease. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis, Lipid peroxidation induces cholesterol domain formation in model membranes. In the case of lipid mobility, this principle is exemplified by the observation that decreasing the excessive lipid mobility in LGMD2B patient cells using a membrane permeant modified glucocorticoid improves repair (Sreetama et al., 2018). Stem cells in animal models of regeneration. To do so, they must control the movement of liquids across their boundaries. Rac1, a Rho family GTPase required for repair (Verboon & Parkhurst, 2015), forms nanoclusters at sites enriched in PA and PIP3, whose roles in regulating Rac1 appear to be non-overlapping (Maxwell et al., 2018). How does the cell membrane self heal? Thus, DAG acts as a scaffold that initiates and coordinates downstream signaling pathways within a tight spatial and temporal window rather than as a marker of membrane injury for fast-acting structural proteins. Use of lipidomics during epidermal wound repair identified that several of the plasma membrane lipids discussed above are enriched during wound repair. 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). Muscle fibers have a complex plasma membrane network with a repeating register of deep plasma membrane invaginations called the t-tubule network. Stem cell medicine brings a new paradigm to modern medicine which has relied heavily on medicine or surgery. The .gov means its official. In. The fatty membranes of cells are capable of self-repair using a mechanism that involves calcium-dependent exocytosis. FOIA This may allow these lipids and proteins to interact with new partners that were unavailable due to spatial segregation prior to injury. Verweij FJ, Revenu C, Arras G, Dingli F, Loew D, Pegtel DM, Zimmermann P (2019). The plasma membrane separates the extracellular environment from the cell interior, where biochemical reactions necessary for life occur. Cell Calcium. The precise role of EHD2 in membrane repair is not known, although it is known as a membrane shaping protein that may be involved in membrane fusion (Campelo, Fabrikant, McMahon, & Kozlov, 2010). Spiders turn liquid into a strong, stretchy fiber by squeezing it through a small space that helps protein molecules to connect with eachother. Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. In response to increased stress on the plasma membrane, caveolae have been proposed to act as mechanosensors, buffering membrane tension in response to mechanical stress (Cheng et al., 2015; Sinha et al., 2011). Moissoglu K, Kiessling V, Wan C, Hoffman BD, Norambuena A, Tamm LK, & Schwartz MA (2014). Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, & Jaiswal JK (2014). In mammalian cells, lipids formed upon the phosphate and glycerol (e.g. Importantly, sequestration of cholesterol alone increased PLD activity, supporting the idea that transient increase in lipid fluidity after membrane injury may be required for PLD-mediated signaling. Sci Rep. 2023 Mar 23;13(1):4763. doi: 10.1038/s41598-023-31973-2. They break down excess or worn-out cell parts. Lenhart KC, ONeill TJ, Cheng Z, Dee R, Demonbreun AR, Li J, Taylor JM (2015). Unlike sharks or alligators, for example, whose teeth are generally all the same size and shape, mammals have differently shaped teeth in different areas of the jaws to target specific foods or foraging strategies. In addition to PA, PG is another lipid product of PLD activity relevant to membrane repair, and its synthesis has been implicated in the process of membrane repair and repair of epithelial wounds (Arun et al., 2013; Piazza & Marmer, 2007). Liquids, mostly water, make up 70 to 90% of all living systems, and the loss of even a small percentage can mean the difference between life and death.
Membranes Self-repair Biological Strategy AskNature 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). Shear stress on the plasma membrane also results in the dissociation of the negative regulator RhoGDI and its binding partner Rho (Shao et al., 2018). 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. Ligeti E, Dagher M-C, Hernandez SE, Koleske AJ, & Settleman J (2004).
How Phospholipids Help Hold a Cell Together - ThoughtCo This structural arrangement is important for the organization of cholesterol in biological membranes as it results in the hydroxyl group associating with the neighboring lipid head groups and water, while the majority of the cholesterol molecule resides within the hydrophobic core of the membrane. Muscle membrane integrity in Duchenne muscular dystrophy: recent advances in copolymer-based muscle membrane stabilizers. Nam D. Jan 28, 2018 Because it has the Golgi apparatus Explanation: Actually it doesn't heal by itself it is helped by a cell organelle named Golgi apparatus. 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. However, to successfully repair the cell also needs to restore the barrier function of the resealed membrane. Thus, each of these lipids contributes significantly to the organization, structure, and function of the plasma membrane as a whole. Membrane damage: Damage to the cell membrane disturbs the state of cell electrolytes, e.g. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. Stem cell extracellular vesicles: extended messages of regeneration, Annual review of pharmacology and toxicology. Cambridge (MA): Harvard Stem Cell Institute; 2008. 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). Van Meer G, Voelker DR, & Feigenson GW (2008). Eukaryotic cells have been confronted throughout their evolution with potentially lethal plasma membrane injuries, including those caused by osmotic stress, by infection from bacterial toxins and parasites, and by mechanical and ischemic stress. These examples of organizational heterogeneity, along with the differences among the lipids that comprise the plasma membrane confer a variety of structural and signaling properties to the plasma membrane and allow the plasma membrane to mount and sustain localized signaling despite being fully interconnected and fluid. Similar to the changes in tension described above, the fluidity of the plasma membrane is also dynamic after injury. This preferential association between different lipids results in an important feature of the plasma membrane its transverse and lateral heterogeneity. Calcium can activate proteins directly, and ultimately is the initiator of many downstream repair pathways. PIP2 accumulation was observed as early as 4 seconds in mouse myofibers; however, it continued to accumulate even 1 minute post-injury suggesting a role in the later stages of repair (Demonbreun et al., 2016). For example, replacement of a cylindrical lipid (e.g. The organization of lipids within the membrane also affects the structure of underlying cortical cytoskeleton. 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. Such a role of CLIC/GEEC-mediated endocytosis in membrane remodeling is also supported by the observation that CLIC/GEEC is immediately activated in response to decreased membrane tension and has the capacity to turn over large amounts of plasma membrane (Thottacherry et al., 2018). In response to an injury, a sudden change in hydrostatic pressure and local disassembly of the cortical cytoskeleton causes a rapid drop in membrane tension (Jaiswal et al., 2014; Miyake, McNeil, Suzuki, Tsunoda, & Sugai, 2001; Togo et al., 2000). Using these dating methods, it was inferred that fat cells (adipocytes) replace at a rate of 86% per year (BNID 103455). In this review, we have discussed how lipids working at the individual as well as at the population level facilitate the proper orchestration of the repair response.
Regulation of actin binding proteins by PIP2 occurs in part through electrostatic interactions (Senju et al., 2017), suggesting that clusters of PIP2 molecules may be necessary to achieve build-up of F-actin itself. 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). This is achieved in part through the activity of lipid modifying enzymes, such as phospholipases, which are activated by the changing biochemical environment after injury. Role of calcium-sensor proteins in cell membrane repair. See this image and copyright information in PMC. sharing sensitive information, make sure youre on a federal Requirement for annexin A1 in plasma membrane repair, Repairing a torn cell surface: make way, lysosomes to the rescue, Plasma membrane disruption: repair, prevention, adaptation, Annual review of cell and developmental biology, Coping with the inevitable: how cells repair a torn surface membrane, Biochemistry of lipids, lipoproteins and membranes. 2023 Apr 4;122(7):1355-1363. doi: 10.1016/j.bpj.2023.03.001. An official website of the United States government. This is due to their lack of integration into the membrane under normal lipid packing conditions. In this case, cholesterol actually increases the fluidity among these lipids, which prevents them from forming a gel-like phase that is incompatible with the overall fluid nature of the plasma membrane (Krause & Regen, 2014). Gradients of Rac1 nanoclusters support spatial patterns of Rac1 signaling. These examples illustrate the far-reaching consequence of lipid movement on structural stability of the plasma membrane and its ability to successfully repair. For example, Annexin 5 accumulates first to form a lattice structure, which provides a force opposing the tension at the wound edge (Bouter et al., 2011). However, lipid signaling also helps to coordinate downstream repair pathways that result in the membrane trafficking and cytoskeletal reorganization required for repair. Further, PE and PC head groups can be cleaved and replaced with serine to produce PS (Oropeza, 2017). Accessibility The https:// ensures that you are connecting to the Prior to increase in shear force, PLD associates with lipid rafts, physically segregated from its activator PIP2 and its substrate PC (Petersen et al., 2016). While no defined roles for PA after membrane injury are known, PA has been observed to rapidly appear at the wound edge (Vaughan et al., 2014), which fits with the fast (650 s) timescale of PA generation by PLD (Petersen et al., 2016). 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). The plasma membrane itself forms the barrier responsible for the hydrostatic pressure experienced by the cell, while the cortical actin cytoskeleton, focal adhesions, and extracellular matrix regulate the structural tension (Burridge & Guilluy, 2016; Gauthier et al., 2012). 2022 Aug 4;11:e80778.
Sealing holes in cellular membranes | The EMBO Journal 2008 Mar 10;180(5):905-14. doi: 10.1083/jcb.200708010.
Plasma membrane integrity in health and disease: significance and Cell membrane | Definition, Function, & Structure | Britannica GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice. One of the roles of lipid mobility may be to allow for the movement of individual lipids to form microdomains near the site of injury, which has been shown to be important for repair (Vaughan et al., 2014), perhaps by facilitating lipid-mediated signaling. A surprise arrived when heart muscle cells were analyzed. Lamb RG, Harper CC, McKinney JS, Rzigalinski BA, & Ellis EF (1997). The structural role of lipids may extend into the signaling role, which can then impact back on the structural characteristics of the repairing membrane by changing the composition or distribution of individual lipids. This mechanism is particularly intriguing in light of the redox-sensitive nature of MG53. While reassembly of the cortical cytoskeleton in the minutes following injury is known to restore membrane tension (described in Section 3.3), membrane remodeling also contributes to increasing tension. Thus, electrostatic interaction with signaling lipids helps to facilitate GTPase localization, which is a critical feature that determines the efficiency and magnitude of the downstream response (Das et al., 2015; Yogurtcu & Johnson, 2018). Individual lipids can serve as signaling molecules on their own or through binding proteins, and chemical changes to a single lipid can initiate change in local membrane composition. 1Childrens National Health System, Center for Genetic Medicine Research, 111 Michigan Avenue NW, Washington, DC 20010-2970 USA, 2Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC USA. Epub 2023 Mar 3. Unlike phospholipids and sphingolipids, which are structurally analogous, cholesterol is composed of a steroid backbone that results in a planar and more rigid molecule. The structural role of lipids described above illustrates how their ability to modify the biophysical properties of the plasma membrane is beneficial for resealing. Jimenez AJ, Maiuri P, Lafaurie-Janvore J, Divoux S, Piel M, & Perez F (2014). Muscle fibers are subject to huge variations in membrane tension, due to their contractile activity. This suggests the possibility that caveolae could act as mechanosensors that facilitate adaptation to membrane injury through gene transcription, although this remains to be explored. However, shear force on the membrane increases the kinetic energy required for lipid mixing (i.e. For example, a scallop prevents structural failure from fracture because its shell is comprised of two materials of varying stiffness. The calcium influx, Survival from bacterial pore-forming toxins, Survival from bacterial pore-forming toxins utilizes both exocytic and endocytic responses. Healing, Examples of self-repairing cells. (2013). Dysferlin is not detected at injury sites until 10 s postinjury, a delay we attribute to an intermediary step involving calpain cleavage. Like the exterior walls of a house, the . What's found inside a cell. Spatiotemporal dynamics of actin remodeling and endomembrane trafficking in alveolar epithelial type I cell wound healing. Regulation of Rac1 translocation and activation by membrane domains and their boundaries, Stressing caveolae new role in cell mechanics, Membrane cytoskeleton: PIP2 pulls the strings, The FluidMosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years, Biochimica et Biophysica Acta (BBA)-Biomembranes. They include glycerophosphocholines, glycerophosphoglycerols, glycerophosphoinositols, as well as triacylglycerols (Taverna, Nanney, Pollins, Sindona, & Caprioli, 2011). The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity.
Membrane Healing 2022 Dec 1;11(1):38. doi: 10.1186/s13619-022-00141-8. Federal government websites often end in .gov or .mil. Further, PA is implicated in processes critical to the success of membrane repair such as vesicle fusion with the plasma membrane and GTPase signaling (Cazzolli et al., 2006; Zhang & Du, 2009).
3.1 The Cell Membrane - Anatomy & Physiology doi: 10.1016/j.cub.2017.12.034. The Importance of Pore-Forming Toxins in Multiple Organ Injury and Dysfunction. Similar inter-leaflet heterogeneity exists among sphingolipids, with the glycosphingolipids maintained exclusively in the outer leaflet. (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). Rapid actin-cytoskeletondependent recruitment of plasma membranederived dysferlin at wounds is critical for muscle membrane repair. Small GTPases, such as Rho family members, associate with biological membranes via lipid modifications (ten Klooster & Hordijk, 2007); however, selectivity for the plasma membrane is regulated through the polybasic domain comprised of a cluster of positively charged amino acids (Do Heo et al., 2006; Maxwell, Zhou, & Hancock, 2018). Abstract. Lipid domaindependent regulation of single-cell wound repair, Rho family GTPases bring a familiar ring to cell wound repair. In some cases, these forces are benign, such as membrane protrusion driven by cortical actin polymerization (Pontes, Monzo, & Gauthier, 2017). In addition to working on their own, lipids also interact with proteins to coordinate these processes. 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). The .gov means its official. calcium, which when constantly increased, induces apoptosis. This raises the intriguing possibility that MG53 may affect plasma membrane structural properties. However, excessive force applied to the membrane can result in physical damage, such as the shear force applied on the endothelial cells by blood flow, on muscle cells during contraction, on lung alveolar cells during breathing, or by a blunt force trauma to any cell (Cong, Hubmayr, Li, & Zhao, 2017; Demonbreun & McNally, 2016; McNeil & Steinhardt, 2003).