Cellular organelles and structure (article) | Khan Academy At each of these levels the structural and signaling aspects of lipids are critical for the cell to mount an efficient response to plasma membrane injury. An official website of the United States government. 2013 Dec 19;(82):e50848. The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. The discussion above illustrates several roles for lipids in changing biophysical properties of the injured plasma membrane during repair. 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). Cell walls provide structural support for the cell. A decrease in membrane tension precedes successful cell-membrane repair. eCollection 2021. Delivery of membrane (i.e. PA is then used to create other phospholipids including PI, PC, PS, and PE, through the use of the DAG backbone. In contrast to PC, sphingomyelin forms a taller and narrower cylinder, which along with the configuration of its acyl chains, allowing this lipid to pack more tightly than phospholipids (Cebecauer et al., 2018). Cells defend themselves from viruses, bacteria with armor of protein Constitutive fusion of biosynthetic vesicles is a major mechanism for delivery of new lipids and proteins, which helps to build and maintain the plasma membrane. (2009). 2018 Apr 23;28(8):R392-R397. The primary plasma membrane sphingolipid in mammalian cells is sphingomyelin, which utilizes a ceramide backbone (Merrill Jr, 2008). This allows local and functional diversity between the two leaflets as well as various parts of the single contiguous plasma membrane (Figure 2B). Plasma membrane damage increases the fluidity of individual lipids, allowing them more freedom to migrate laterally, rotate, or even flip appearing in the opposite leaflet of the membrane. An organelle (think of it as a cell's internal organ) is a membrane bound structure found within a cell. Plasma membrane lipids containing the alkanoamine sphingosine are called sphingolipids. Zhang KS, Blauch LR, Huang W, Marshall WF, Tang SKY. (2017). The primary method for PIP2 formation in cells is by the activity of PI(4)P-5 kinase (PI5K) (Kolay, Basu, & Raghu, 2016). government site. Hall ED, Wang JA, Miller DM, Cebak JE, & Hill RL (2018). doi: 10.7554/eLife.80778. The plasma membrane, also called the cell membrane, is the membrane found in all cells that separates the interior of the cell from the outside environment. Shed microvesicles containing streptolysin-O have been shown to also contain annexins A1 and A6 (219). Skalman LN, Holst MR, Larsson E, & Lundmark R (2018). 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. Membrane injury causes a local influx of calcium and activation of calpains. 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). Nojima H, Freeman CM, Gulbins E, & Lentsch AB (2015). Within a single leaflet, lateral heterogeneity is found in the form of lipid microdomains, such as the cholesterol and sphingolipid-rich domains that serve as signaling platforms to accumulate plasma membrane-associated proteins. While much attention has been paid to the involvement of proteins in the membrane repair pathway, the role of lipids in facilitating plasma membrane repair remains poorly studied. Despite the many different types of tissue, there is a common repair program involved in tissue repair. Careers. 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. Inositol is bound to the phosphate group in this phospholipid. Before Furthermore, exposure of the plasma membrane hydrophobic core as a result of reduced lipid packing provides the opportunity for injury-triggered lipid signaling through the binding of cholesterol (see Section 4). Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo. 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. Int J Mol Sci. 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. Inherent plasticity and microfracture toughening mechanisms work together to prevent antlers from breaking. 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. sharing sensitive information, make sure youre on a federal 2022 Aug 4;11:e80778. 2023 Apr 4;122(7):1355-1363. doi: 10.1016/j.bpj.2023.03.001. Similar to the changes in tension described above, the fluidity of the plasma membrane is also dynamic after injury. The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity. Vaughan EM, You J-S, Yu H-YE, Lasek A, Vitale N, Hornberger TA, & Bement WM (2014). The Biomimicry Institute empowers people to create nature-inspired solutions for a healthy planet. 2021 The Biomimicry Institute. Eukaryotic cells have been shown to utilize calcium-activated exocytosis to reduce membrane tension and promote repair via lipid-disorder driven attractions. 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). It is unclear what role, if any, that IP3 may have in repair, but its role in calcium signaling and the fact that injured cells secrete IP3 for hours post-injury (Lamb et al., 1997) suggest a possible signaling role in repair that may extend beyond the process of membrane resealing, which needs further investigation. While lipids are often ascribed a metabolic role as energy storage molecules, they also play important structural and signaling roles in the cell. Caveolinopathies: from the biology of caveolin-3 to human diseases, Annexins: linking Ca 2+ signalling to membrane dynamics, Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-45-bisphosphate. Trends Cell Biol. Calcium entry after plasma membrane injury is required for repair. Plasma membrane lipids and proteins interact with the extracellular matrix (ECM) and the cortical actin network, both of which provide sources of tension that support the structure of the membrane. Instead, there exists distinct inter- and intra-leaflet heterogeneity of lipids. Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, & Jaiswal JK (2014). In addition to regulating the patterning and activity of Rho family GTPases, lipids also have a more direct role in regulating F-actin association with the plasma membrane. Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. (B) The plasma membrane is not a homogenous mixture of proteins and lipids (as in A). Lysosomes are involved with various cell processes. sharing sensitive information, make sure youre on a federal They may be used to destroy invading viruses and bacteria. Pollet H, Conrard L, Cloos A-S, & Tyteca D (2018). We will highlight how lipids respond to injury and facilitate repair both at the level of individual molecules and at the bulk level by collectively altering the plasma membrane form and function. Each of these provides another mechanism for generating specific membrane lipids acutely in parallel to biosynthetic inputs. Another critical shared feature is a set of highly-specialized teeth. This cell membrane provides a protective barrier around the cell and regulates which materials can pass in or out. It also holds the potential for new applications and therapeutic approaches for treating human disease. Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D, Conversion of phosphatidylcholine to phosphatidylglycerol with phospholipase D and glycerol, Journal of the American Oil Chemists Society. Exocytic fusion reduces membrane tension, and vesicle-vesicle fusion events provide a patch as a replacement for the membrane barrier missing at the disruption site. This Goldilocks principle applies to several aspects of lipid involvement in the repair process. Clipboard, Search History, and several other advanced features are temporarily unavailable. The plasma membrane is a dynamic barrier that separates the cell interior from the extracellular space (Figure 2C). Along with the annexins, which act quickly to physically manipulate the membrane itself, reassembly of the cytoskeleton plays a crucial role in restoring membrane tension in the later stages of repair. The plasma membrane has a unique lipid composition that helps distinguish its structural and functional properties from the other internal membrane-bound compartments. The physical and molecular mechanisms by which a cell can heal membrane ruptures and rebuild damaged or missing cellular structures remain poorly understood. Sphingolipids in liver injury, repair and regeneration, Development of Biomimetic Membrane Assemblies on Microspheres for High-Throughput and Multiplexable Studies, Caveolae as plasma membrane sensors, protectors and organizers. Gauthier NC, Masters TA, & Sheetz MP (2012). Copyright 2017, American Association for the Advancement of Science. The site is secure. While initial loss of cortical actin aids in repair by allowing physical access for vesicles to fuse with the plasma membrane, the accumulation of F-actin at the injury site in the minutes following injury, is also required to provide structural support to the repairing/repaired membrane and prevent additional injury due to membrane fragility (Demonbreun et al., 2016; Horn et al., 2017; Jaiswal et al., 2014; McDade, Archambeau, & Michele, 2014; Miyake et al., 2001). Sterols, or steroid alcohols, are a third type of plasma membrane lipid, with cholesterol being the predominant form found in mammalian cells. Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins. Furthermore, individual lipids may be modified by proteins, which generate new lipid species that can change membrane structural properties (red, Cer) or be used for signaling (purple, DAG). This study showed that shear force on the membrane, as experienced by cells during mechanical injury, facilitated increased PLD activity through the process of lipid mixing. Failure or delay in these processes, as in chronic inflammatory conditions and conditions of regenerative deficit would lead to aberrant tissue remodeling resulting in fibrotic or adipogenic replacement of the lost tissue. These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Slabodnick M, Prevo B, Gross P, Sheung J, Marshall W. J Vis Exp. 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). F-actin accumulation is also responsible for providing support to the newly resealed membrane, restoring tension, and preventing subsequent injury. A single cell is often a complete organism in itself, such as a bacterium or yeast. Similarly, peak PIP2 accumulation at the injury site occurred 45 seconds post-injury in Xenopus oocytes (Vaughan et al., 2014). (D) The lipid make-up of the plasma membrane constantly changes. Given their integral role in forming the structural backbone of the membrane, lipids are ideally placed to act as damage sensors, initiating early signaling that sets the stage for subsequent repair machinery. Thus, local lipid peroxidation may provide transient membrane stabilization, while mechanisms such as redox-dependent MG53 binding may limit the spread of lipid peroxides. This Review presents current understanding in wound healing and regeneration as two distinct aspects of cellular self-repair by examining a few model organisms that have displayed robust repair capacity, including Xenopus oocytes, Chlamydomonas, and Stentor coeruleus Although many open questions remain, elucidating how cells repair themselves is important for our mechanistic understanding of cell biology. What is Mitosis? | Let's Talk Science ESCRT machinery is required for plasma membrane repair. Charged phospholipids such as PIP2, PS, and PE are almost exclusively found on the inner leaflet, while the glycosphingolipids are only found on the outer leaflet. This homeostatic process of vesicle fusion that maintains the plasma membrane at rest also enables plasma membrane repair through regulated fusion of vesicles triggered by calcium influx following plasma membrane injury (Horn & Jaiswal, 2018; McNeil & Steinhardt, 2003). While it is unclear whether caveolae can provide structural assistance to the damaged membrane in the context of a large membrane injury (as opposed to sub-injury threshold stress, (Sinha et al., 2011)), caveolae may still provide a signaling function during the repair process. 2008 Mar 10;180(5):905-14. doi: 10.1083/jcb.200708010. How skin heals is a good example of the role of cellular processes. Furthermore, ASM activity at the injury site would locally produce ceramide from sphingomyelin. Heier CR, Damsker JM, Yu Q, Dillingham BC, Huynh T, Van der Meulen JH, Scheffer L. (2013). This results in the replacement of half of the body's adipocytes in 8 years. Lipids act as signaling molecules through their ability to directly bind or otherwise alter the activity or localization of target proteins (Figure 2B, ,C).C). Modular, cascade-like transcriptional program of regeneration in, R01 GM113602/GM/NIGMS NIH HHS/United States. Please enable it to take advantage of the complete set of features! official website and that any information you provide is encrypted 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). This involves a series of distinct, but mutually dependent stages including inflammation, regeneration, and remodeling of the tissue (Gurtner, Werner, Barrandon, & Longaker, 2008). The plasma membrane is semi-permeable, allowing the cell to communicate with and utilize resources from its surrounding environment. Accumulation of GRAF1 at the repair site occurs 2 minutes after injury, supporting its potential role in membrane remodeling following resealing. Membrane repair is a conserved physiologic process in multiple tissues Organ Type of mechanical force Principal cells stressed Cell wounding Calcium-activated exocytosis reduces membrane tension and promotes spontaneous repair driven by lipid disorder for injuries hundreds of nanometers in diameter. and transmitted securely. 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). and transmitted securely.