MIT chemists have uncovered a fascinating new insight into the role of cell membranes, challenging long-held beliefs about their function. The study, published in the journal eLife, reveals that cell membranes not only provide structure and protection but also actively influence the behavior of embedded protein receptors, particularly the Epidermal Growth Factor Receptor (EGFR).
The research, led by Gabriela Schlau-Cohen, demonstrates that the composition of the cell membrane can significantly impact the function of EGFR, a receptor crucial for controlling cell growth. By altering the concentration of negatively charged lipids in the membrane, the team discovered that they could lock EGFR into an overactive state, promoting uncontrolled cell proliferation. This finding offers a potential explanation for why cancer cells with high lipid levels exhibit aggressive growth characteristics.
Schlau-Cohen emphasizes the paradigm shift in our understanding of membrane function, stating, 'The longstanding dogma of what a membrane does is that it's just a scaffold, an organizational structure. However, there have been increasing observations that suggest that maybe these membrane lipids are actually playing a role in receptor function.'
The study's approach involved using nanodiscs, self-assembling membranes that mimic the cell membrane, allowing researchers to study the full-length receptor. By employing single-molecule FRET (fluorescence resonance energy transfer), they could measure the distance between different parts of the protein and observe how its shape changes under various conditions. This technique revealed that elevated levels of negatively charged lipids in the membrane trigger a constant, active conformation of EGFR, regardless of ligand binding.
Furthermore, the research explored the role of cholesterol in EGFR function. The team found that increased cholesterol levels in the membrane made the membranes more rigid, suppressing EGFR signaling. This discovery opens up new avenues for cancer treatment, suggesting that neutralizing the negative charge in the membrane might downregulate EGFR signaling, potentially slowing down tumor growth.
This groundbreaking study highlights the dynamic nature of cell membranes and their profound influence on receptor function. It challenges the traditional view of membranes as passive structures and paves the way for innovative therapeutic strategies targeting membrane composition to combat cancer and other diseases.
