High Hydrostatic Pressure Induces a Lipid Phase Transition and Molecular Rearrangements in Low‐Density Lipoprotein Nanoparticles

Abstract

Low-density lipoproteins (LDL) are natural lipid transporter in human plasma whose chemically modified forms contribute to the progression of atherosclerosis and cardiovascular diseases accounting for a vast majority of deaths in westernized civilizations. For the development of new treatment strategies, it is important to have a detailed picture of LDL nanoparticles on a molecular basis. Through the combination of X-ray and neutron small-angle scattering (SAS) techniques with high hydrostatic pressure (HHP) this study describes structural features of normolipidemic, triglyceride-rich and oxidized forms of LDL. Due to the different scattering contrasts for X-rays and neutrons, information on the effects of HHP on the internal structure determined by lipid rearrangements and changes in particle shape becomes accessible. Independent pressure and temperature variations provoke a phase transition in the lipid core domain. With increasing pressure an inter-related anisotropic deformation and flattening of the particle are induced. All LDL nanoparticles maintain their structural integrity even at 3000 bar and show a reversible response toward pressure variations. The present work depicts the complementarity of pressure and temperature as independent thermodynamic parameters and introduces HHP as a tool to study molecular assembling and interaction processes in distinct lipoprotein particles in a nondestructive manner.

Cellular transfection using rapid decrease in hydrostatic pressure

“…In accordance with Le Châtelier’s principle, increasing pressure appears to induce cells to adapt to a smaller hydrodynamic volume 11 , 42 . With respect to the cellular transfection observed, such pressure-induced effects may act through the alteration of existing structural voids, particularly at sites where different biomolecular isotypes interdigitate; such as the integral membrane proteins and membrane phospholipids 20 , 43 .…”

“…Within the range of 0.1–100 MPa 9 , 17 , phospholipid bilayers undergo phase transition from a fluid-crystalline state to a more ordered gel-like conformation, with the lipid headgroups being relatively incompressible compared to the bilayer interior 17 , 18 . As a result of this elevated pressure, the packing density of lipid chains increases leading to enhancement of membrane thickness and a concomitant decrease in the cross-sectional area of the lipid chain 19 , 20 . Thus with increasing pressure, phospholipid acyl chains become more ordered and the void volumes between lipids decreases, giving rise to the negative volume changes observed for these transitions 21 .…”

Effect of high‐hydrostatic pressure on the digestibility of egg yolk and granule

“…This difference could be explained by the lower temperature used during the centrifugation step of egg yolk since lipid extraction yield is improved with increased temperature (Price et al, 2018;Sivaramakrishnan & Incharoensakdi, 2019). Globally, literature shows relative high resistance of lipid complexes such as LDLs and HDLs toward high pressure (Golub et al, 2017;Lehofer et al, 2018;Speroni et al, 2005) validating the absence of difference in PL content for the initial stage. Moreover, the stable concentration of phospholipids during gastric and intestinal phases for control and EPY and granule could be related to the resistance of phosphatidylethanolamine and phosphatidylcholine, the main egg yolk phospholipids, to digestion (Mrsny et al, 1986).…”

High-pressure adaptation of extremophiles and biotechnological applications

“…Recent studies on human plasma lipoproteins under HHP revealed a reduced flexibility and higher compressibility of its triglyceride rich form, the form associated to pathological health conditions [61,62]. Overall, eukayotes are more pressure-sensitive than prokaryotes and piezosensitive bacilli and spiral-shaped bacteria are inactivated at lower pressures than cocci [39,64].…”