Kluge, C. | bioRxiv Science

bioRxiv2022

Lipid bicelles in the study of biomembrane characteristics

Simulations of lipid membranes typically make use of periodic boundary conditions to mimic macroscopically sized membranes and allow for comparison to experiments performed e.g. on planar lipid membranes or on unilamellar lipid vesicles. However, the lateral periodicity partly suppresses membrane fluctuations or membrane remodeling, processes that are of particular importance in the study of asymmetric membranes - i.e. membranes with integral or associated proteins and/or asymmetric lipid compositions. Here, we devised a simple albeit powerful lipid bicelle model system that (i) displays similar structural, dynamical and mechanical properties compared to infinite periodic lipid membrane systems, and allows (ii) for the study of asymmetric lipid bilayer systems, and (iii) the unperturbed formation of local spontaneous curvature induced by lipids or proteins in coarse-grained and all-atom molecular dynamics simulations. In addition, the system is characterized by largely unbiased thermal fluctuations as opposed to standard bilayer systems. Application of the bicelle system for an asymmetric lipid composition resembling the plasma membrane reveals that the cholesterol density for a tension-free plasma membrane with a vanishing spontaneous curvature is larger by 28% within the extracellular leaflet compared to the cytosolic leaflet. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/517649v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@56cb44org.highwire.dtl.DTLVardef@3b16faorg.highwire.dtl.DTLVardef@161a143org.highwire.dtl.DTLVardef@a248e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development

Fertility rates in the developing world have dramatically dropped in the last decades. This drop is likely due to a decline in sperm quality and women having children at older ages. Loss of function mutations in DJ-1, a Parkinsons associated gene, are linked to alterations in multiple cellular processes such as mitochondrial activity, ROS production or sperm motility and lead to an early onset of Parkinsons disease and male infertility in humans and other species. Glycolate (GA) and D-lactate (DL), products of DJ-1 glyoxalase activity, sustain mitochondrial function and protect against environmental aggressions. We, therefore, tested whether these substances could also have a rescue effect on these phenotypes. Here, we show that DJ-1 loss of function not only affects sperm motility but also leads to defects in mitosis and an age-dependent increase in the abortion rate. Remarkably, whereas DL was only able to rescue embryonic lethality in C. elegans, GA rescued these phenotypes in all model systems tested and even increased sperm motility in wild-type sperm. These positive effects seem to be mediated through an increase in NAD(P)H production and the regulation of intracellular calcium. These findings not only strongly suggest GA as a new therapeutic candidate to improve male and female fertility but also show its potential to treat diseases associated with a decline in mitochondrial function or to improve mitochondrial function in aging.

developmental biology↗