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. 2018 Aug;53:44-51.
doi: 10.1016/ Epub 2018 May 19.

Cellular Mechanisms of Physicochemical Membrane Homeostasis

Free PMC article

Cellular Mechanisms of Physicochemical Membrane Homeostasis

Robert Ernst et al. Curr Opin Cell Biol. .
Free PMC article

Erratum in


Biological membranes are vital, active contributors to cell function. In addition to specific interactions of individual lipid molecules and lateral organization produced by membrane domains, the bulk physicochemical properties of biological membranes broadly regulate protein structure and function. Therefore, these properties must be homeostatically maintained within a narrow range that is compatible with cellular physiology. Although such adaptiveness has been known for decades, recent observations have dramatically expanded its scope by showing the breadth of membrane properties that must be maintained, and revealing the remarkable diversity of biological membranes, both within and between cell types. Cells have developed a broad palette of sense-and-respond machineries to mediate physicochemical membrane homeostasis, and the molecular mechanisms of these are being discovered through combinations of cell biology, biophysical approaches, and computational modeling.


Figure 1
Figure 1. Physicochemical membrane homeostasis
(A) Classical experiments by Michael Sinensky [5] established that when the membrane of cells (left) becomes less fluid upon a drop of temperature (middle), cells adjust their lipid composition to reestablish membrane fluidity (right). (B) Physicochemical membrane properties can direct differentiation processes [22]. Mesenchymal stem cells can differentiate into fat cells or osteoblasts (left). The PMs of these cells show lineage-specific lipidomic remodeling affecting membrane phase behavior (middle), with osteoblast PMs characterized by a higher polyunsaturated lipid content and higher tendency to phase segregate. Mimicking the compositional and biophysical remodeling of the PM by supplementation with polyunsaturated fatty acid (DHA) directs osteoblast differentiation (right).
Figure 2
Figure 2. Fundamental mechanisms of membrane property sensors
(A) Sensing at membrane surfaces: Proteins can sense the properties of the membrane surface via lipid packing defects that promote folding and inserting amphipathic helices into the interfacial region of a membrane. Lipid packing defects are indicated as voids between schematically illustrated lipid molecules and increased packing densities are denoted by darker shading of the bilayer. Oxygen atoms are shaded red. Exemplary hydrophobic residues inserting into lipid packing defects are indicated. (B) Sensing within the membrane core. A lipid packing sensor from yeast senses packing of the membrane core to control membrane fluidity [17]. The mechanism involves a selection of distinct rotational conformations driven by membrane environment. (C) Sensing across the lipid bilayer. Membrane compressibility, an important property affecting membrane protein sorting along the secretory pathway, can be sensed only across the lipid bilayer. The transducer or the unfolded protein response, Ire1, senses membrane rigidity and thickness by locally deforming the bilayer, leading to membrane-mediated oligomerization in a stressed ER membrane [20].

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