Lipid Rafts in Disease & Therapeutics
Lipid rafts are closely-packed assemblages of lipids, cholesterol, and proteins that float within the lipid bilayer of cellular membranes. Their structure and composition makes them essential to many cellular processes, including cell signaling and communication, molecular transport across membranes, and modulating membrane fluidity. As such, these formations are being explored both as therapeutic targets for diseases from cancer to viral infections, as well as avenues for improving drug delivery.
Cancer
As lipid rafts are critical components of cell metabolism, signaling, and mobility, their dysregulation can lead to a variety of disease states. In cancer cells, lipid rafts are not only more prevalent than in normal cells, but they also contain many proteins and receptors involved in regulating oncogenic pathways and apoptosis (cell death). Lipid rafts can cluster into larger structures with distinct signaling functions, such as clusters of apoptotic signaling molecule-enriched rafts (CASMERs). Additionally, due to their role in cell migration and adhesion, lipid rafts can facilitate the spread of cancer cells to other tissues and enable metastasis. These apoptosis signaling hubs, as well as migration, adhesion, and dissemination-promoting features of lipid rafts are being studied as potential targets for cancer therapeutics.
Infectious disease
In infectious diseases, lipid rafts modulate host-pathogen interactions by detecting potential pathogens, regulating intra- and extracellular trafficking, and recruiting other cell types involved in immune responses. Lipid rafts act as gatekeepers against diverse viruses, bacteria, and fungi; research shows that inhibiting their formation facilitates cell entry for a variety of pathogens.
However, pathogens are also constantly evolving ways to exploit lipid rafts in order to enter and exit cells, as well as replicate themselves. For example, HIV has been shown to hijack lipid rafts as hubs for viral replication and fusion with host cells, leading to an increase in lipid raft abundance in infected cells. In a 2020 paper, Dubrovsky et al. showed that a protein associated with lipid raft and cholesterol regulation (Apolipoprotein A-I binding protein, or AIBP) reduced lipid rafts in infected cells and consequently inhibited HIV replication. Modulating pathogen-lipid raft associations is a promising route for treating other infections as well, from Ebola to COVID-19.
Targeted drug delivery
No matter how effective a therapy is in a test tube, it needs to be taken up by a cell to be medically useful. Researchers are targeting lipid rafts as a way to ensure successful uptake of their therapy of choice. In a 2024 study, Peruzzi et al. demonstrated that specially designing proteins to associate with lipid rafts can improve extracellular vesicle (EV) loading and delivery of desired cargo, in this case a transcription factor engineered to modulate gene expression. In order to design these proteins, the authors used bioinformatic analysis tools to examine structural features found in lipid raft- and EV-associated proteins, optimizing for cargo loading and functional delivery. By leveraging the natural properties of lipid rafts and associated molecules, researchers can continue to improve targeting for a variety of therapeutic modalities.
Conclusion
The cell membrane is much more than a flexible, semi-permeable envelope that separates one cell from another. Microdomains known as lipid rafts help make the cell membrane a hub for molecular exchange and intracellular communication. Honing in on these small, dynamic aggregates of lipids, cholesterol, and proteins will continue to fine-tune our understanding of the pathology and treatment of many diseases.
How can Watershed help your team unlock the secrets of lipid rafts in health, disease, and therapeutics? Whether you are exploring complex proteomics datasets to design a functionally optimized protein or using public clinical data to derive new insights, the Watershed Bio platform has everything your team needs to collaborate, innovate, and drive science forward. Connect with us today to learn more.