Chapter Four - Structural and signaling role of lipids in plasma membrane repair
Introduction
The plasma membrane separates the extracellular environment from the cell interior, where biochemical reactions necessary for life occur. The plasma membrane is semi-permeable, allowing the cell to communicate with and utilize resources from its surrounding environment. However, all cells are susceptible to plasma membrane damage, which results in the mixture of the intracellular and extracellular milieu and can result in death if the damage is not rapidly repaired. Plasma membrane repair relies on the coordinated activity of repair machinery, which carries out membrane fusion, membrane shedding, and polymerization of F-actin at the site of repair (Horn & Jaiswal, 2018). Repair of injured cells is tied closely to tissue repair and regeneration, as shown by studies demonstrating release of inflammatory mediators, including small molecules, peptides and proteins that signal to cells in the inflammatory and regenerative systems to initiate a tissue level reparative response.
The most abundant component of the cell's plasma membrane is the lipids. Lipids are a class of biomolecules, which are generally insoluble in water, and may refer to fatty acids, sterols, mono-, di-, and triglycerides, as well as phospholipids, among others. While with their ability to store energy, lipids are often ascribed a metabolic role, they also play important structural and signaling roles in the cell. Acute and chronic release of lipids and free fatty acids following cell and tissue injury has been widely recognized to be involved in the process of tuning the inflammatory and subsequent tissue repair response. Being the most abundant component of the plasma membrane, lipids are also an essential player in the process of plasma membrane repair; however, much of the research committed to identifying the mechanisms of plasma membrane repair has focused on the proteins associated with plasma membrane repair (Cooper & McNeil, 2015).
Lipids contribute to cellular physiology at both an individual and population level. 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. At the population level, the composition of lipids in a membrane can result in formation of signaling platforms that can change the properties of an entire membrane, enabling the cell to finely tune tension, shape, and rigidity. 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. In this review, we will focus on the role of lipids during plasma membrane repair by discussing their functions as both structural and signaling molecules. 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.
Section snippets
Plasma membrane lipid composition, organization, and response to injury
The plasma membrane has a unique lipid composition that helps distinguish its structural and functional properties from the other internal membrane-bound compartments. Plasma membrane lipids can be grouped into three classes—glycerophospholipids, sphingolipids, and sterols. Each of these lipids contributes their own qualities that affect the structural and signaling characteristics of the plasma membrane (Nicolson, 2014). In mammalian cells, lipids formed upon the phosphate and glycerol (e.g.,
Structural role for lipids during plasma membrane repair
The physical properties of the plasma membrane are governed in large part by the effect of lipid interactions at the population level. 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-Muñoz, Fletcher, & Weiner, 2013; Gauthier, Fardin, Roca-Cusachs, & Sheetz, 2011; Togo, Krasieva, &
Signaling role for lipids during plasma membrane repair
For plasma membrane repair to occur successfully, the cell must possess a means to sense that injury has occurred, coordinate the change in activity and localization of repair machinery, and ultimately close the wounded area. 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. The structural role of lipids described above illustrates
Lipids as a mediator of tissue repair
Failure of injured cells to repair results in cell death and activates a tissue repair response. Despite the many different types of tissue, there is a common repair program involved in tissue repair. This involves a series of distinct, but mutually dependent stages including inflammation, regeneration, and remodeling of the tissue (Gurtner, Werner, Barrandon, & Longaker, 2008). Use of lipidomics during epidermal wound repair identified that several of the plasma membrane lipids discussed above
Conclusion
While often considered to be a passive resident of the plasma membrane, there is ample evidence to support a more active role of lipids in the process of plasma membrane repair as well as tissue repair. 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. These roles of lipids in plasma membrane repair include both a structural role and a signaling role. Rather than these roles being
Acknowledgments
J.K.J. and A.H. acknowledge NIH for financial support—NIAMS (R01AR055686) and NICHD (U54HD090257) and thank our lab members for useful discussions and inputs during the course of writing and editing this work.
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