Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)–related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS counter transport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

Despite numerous strategies involving dynamic covalent bond exchange for dynamic and self-healing materials, it remains a challenge to be able to tune the malleability and self-healing properties of bulk materials through simple small molecule perturbations. Here we describe the use of tunable rates of boronic ester transesterification to tune the malleability and self-healing efficiencies of bulk materials. Specifically, we used two telechelic diboronic ester small molecules with variable transesterification kinetics to dynamically cross-link 1,2-diol-containing polymer backbones. The sample cross-linked with fast-exchanging diboronic ester showed enhanced malleability and accelerated healing compared to the slow-exchanging variant under the same conditions. Our report demonstrates the possibility of transferring small molecule kinetics to dynamic properties of bulk solid material and may serve as a guide for the rational design of tunable dynamic materials.

Lipid droplets (LDs) are found in most cells, where they play central roles in energy and membrane lipid metabolism. The de novo biogenesis of LDs is a fascinating, yet poorly understood process involving the formation of a monolayer bound organelle from a bilayer membrane. Additionally, large LDs can form either by growth of existing LDs or by the combination of smaller LDs through several distinct mechanisms. Here, we review recent insights into the molecular process governing LD biogenesis and highlight areas of incomplete knowledge.Lipid droplets (LDs) are ubiquitous, dynamic cellular organelles that serve as important reservoirs of lipids. These lipids provide energy and serve as substrates for membrane synthesis, making LDs crucial metabolic hubs. Indeed, many of the enzymes that synthesize phospholipids (PLs), triacylglycerols (TGs), and their intermediates, as well as lipases and lipolytic regulators, localize to LD surfaces. In addition to their known role in lipid metabolism, increasing evidence suggests that LDs also participate in protein degradation [1,2], response to ER stress [3], protein glycosylation [4], and pathogen infection [5]. Further details about the general aspects of LD cell biology and physiology are discussed in numerous recent reviews [6][7][8][9][10]. However, despite recent focus and the application of new technologies to study LDs, a number of basic questions remain unanswered. Chief among these are the molecular processes governing how LDs form and grow. Here, we review recent advances in this area. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access LD FormationLDs could either form de novo or could be derived from existing LDs by fission. Most evidence favors the former process as a major source, however, fission of LDs has been observed [24]. De novo formation of LDs in eukaryotes occurs from the ER [25,26], where neutral lipids are synthesized [27]. Precisely how LDs form, however, remains mostly unanswered. Here we present a model for LD formation in three stages ( Figure 1): (1) neutral lipid synthesis, (2) lens formation (intra-membrane lipid accumulation), and (3) drop formation. We highlight recent advances in the understanding of each of these stages.Step 1 Step 3: Droplet FormationAbove a certain size, depending on the oil and phospholipid composition, lipid lenses in the ER are predicted to be unstable and bud, by a mechanism similar to de-wetting, due to thermal fluctuations [6] (Figure 1). The smallest mature cytosolic LDs have diameters in the range of 250-500 nm [21,54], which establishes an upper li...

Here we introduce silyl ether linkage as a novel dynamic covalent motif for dynamic material design. Through introduction of a neighboring amino moiety, we show that the silyl ether exchange rate can be accelerated by almost three orders of magnitude. By incorporating such silyl ether linkages into covalently cross-linked polymer networks, we demonstrate dynamic covalent network polymers displaying both malleability and reprocessability. The malleability of the networks is studied by monitoring stress relaxation at varying temperature, and their topology freezing temperatures are determined. The tunable dynamic properties coupled with the high thermal stability and reprocessability of silyl ether-based networks open doors to many potential applications for this family of materials.

PI4KIIIα is targeted to the plasma membrane via an evolutionarily conserved complex comprised of EFR3 and TTC7 to control PtdIns4P synthesis and the selective enrichment of PtdIns(4,5)P2 in this membrane.