bioRxiv Science⌕ Search

Biology subjects

Campbell, O.

Publications and source records attributed to Campbell, O..

3 recordsLinked to original sources

Cholesteryl Esters Modulate Lipid Droplet Rigidity and Monolayer Organization during Liver Cancer Progression

In mammalian cells, lipid monolayers support the integrity of lipid droplets (LDs), organelles that function as storage for neutral lipids. Liver-targeting illnesses such as liver cancer interrupt normal LD metabolism and prompt changes in the chemical content of these organelles, which can have effects on structural and organizational behavior of the lipids. In LDs, liver cancer induces concentric crystalline phases of cholesteryl esters (CEs) and triglycerides near the NL-monolayer interface, which become more pronounced as CE concentration increases. Yet, there is little known about how this phenomenon may link to persistence of undigested LDs in liver cancer patients. To shed light on this, all-atom molecular dynamics simulations were used to model LD micropipette aspiration experiments and gain insight into the effect of CE concentration on partitioning, structural, and mechanical properties of LDs. We successfully model micropipette aspiration by application of constant surface tension laterally, which stretches lipid bilayers and monolayers as the magnitude increased. The results show increased phospholipid packing due to insertion of CE fatty tails into the monolayer. Increasing CE concentration induces a non-linear change in surface packing defects on the LDs, notable rigidification, and stiffness. Taken together, these insights improve our understanding of the physical properties at the LD monolayer-core interface during liver cancer progression.

biophysics↗

Combining participatory mapping and oral histories of veteran fishers to identify long-term environmental change in a nationally significant river

The detection and monitoring of environmental change is vital for sustainable river management, but historical data are often limited. This study leveraged volunteered geographic information and local ecological knowledge from experienced recreational anglers to identify historical baselines and long-term change in the Rakaia River, a protected catchment under a National Water Conservation Order (WCO) in Aotearoa New Zealand. Oral histories spanning seven decades were recorded using semi-structured interviews with 30 veteran fishers representing 1510 years of combined catchment-specific experience. Inductive thematic analysis and participatory mapping were used to identify physical environment changes and socio-cultural effects associated with recent declines in freshwater fish populations. River environment changes include the loss of natural features such as springs and pools, declines in characteristic native species and habitats, shrinking river mouth la-goon and river plume extents, and interactions with public access. Socio-cultural effects include reduced participation in fishing, community despondence, emotional distress and demographic shifts in fishing hut settlements. Over 20 reported changes involve adverse effects on values that are specifically protected under the WCO, indicative of a policy failure. Declines in multiple indicators of environment health suggest an implementation gap that requires greater attention to environmental monitoring and outcome evaluation yet is hampered by uncertainties around institutional responsibilities. Oral history approaches can help to establish historical baselines for gauging long-term change and enabling adaptive management in this and other data-poor situations.

ecology↗

Lipid-Driven Alignment and Binding of p7 Dimers in Early Oligomer Assembly

Proteins engage in interactions with lipid membranes to facilitate important cellular processes that form the basis of healthy or sick biological conditions. Transmembrane proteins such as ion channels are often made up of bound monomers that engage in specific contacts within the bilayer. However, molecular mechanistic information related to how these channel structures form is scarce. Understanding the role of lipids in driving this process have the potential to close knowledge gaps regarding the assembly behavior of oligomeric proteins which are often clinical targets for disease treatment. Using the hepatitis C virus p7 hexamer as a case study, this work focuses on characterizing the interactions that dictate the beginnings of dimerization using molecular dynamics simulations. Results comparing dimers formed in aqueous solution to those at the surface of a lipid membrane model reveal that protein-lipid interactions are critical in aiding the proper alignment and binding of inter-protein residues. Hydrophobic protein-lipid interactions and hydrogen bonding of key residues to phosphatidylcholine and phosphatidylinositol membrane lipids drive the characteristic inter-protein helix interactions that underlie p7 oligomerization. This increases favorable binding between hydrophobic protein residues, particularly for the first helix of the p7 monomers. This study provides evidence that membrane lipids are a necessary and dynamic factor that contributes to appropriate binding and association of proteins for channel formation within cellular membranes.

biophysics↗