High concentrations of negatively charged lipids in cell membranes can lock the Epidermal growth factor receptor (EGFR) into an overactive state, driving uncontrolled cell proliferation. MIT chemists found that the composition of the lipid membrane directly influences the behavior of embedded protein receptors, challenging the longstanding dogma that membranes serve only as structural scaffolds or protective barriers.
The EGF receptor exists on cells lining body surfaces and organs to control growth. In certain malignancies, specifically lung cancer and glioblastoma, cells overexpress this receptor, which results in uncontrolled division.
How membrane lipids trigger cancer cell growth
The researchers discovered that the lipid environment determines whether a receptor remains active. When a cell membrane contains a higher than normal concentration of negatively charged lipids, EGFR is locked into a state that promotes proliferation.
This mechanism provides a chemical explanation for why cancer cells with these specific lipid profiles enter a highly proliferative state. The membrane doesn’t just hold the receptor in place; it actively modulates the signal the receptor sends into the cell.
Nanodiscs enabled the study of receptor shape
Studying full-length receptors was previously difficult due to the fact that it’s hard to create membranes that allow proteins to span the entire structure while remaining observable. Lead author Shwetha Srinivasan and the team used nanodiscs—self-assembling membranes that mimic natural cell structures—to embed the receptors for analysis.
The team applied single molecule fluorescence resonance energy transfer (FRET) to track the receptor’s physical changes. By labeling different parts of the protein with fluorescent tags, they measured how fast energy traveled between them to determine the exact distance and shape of the receptor under varying conditions.
By neutralizing charges, researchers may treat tumors
Gabriela Schlau-Cohen, the study’s senior author, suggests these findings open a path to new oncology treatments. Neutralizing the negative charge of the cell membrane could potentially turn down EGFR signaling and inhibit tumor growth.
This approach shifts the therapeutic focus from the protein receptor itself to the lipid environment that activates it. Such a strategy could offer an alternative way to manage cancers that are driven by EGFR overactivity.
Which types of cancer overexpress the EGF receptor?
Lung cancer and glioblastoma are specifically identified as types of cancer that overexpress the EGF receptor, which can lead to uncontrolled growth.
What is a nanodisc?
A nanodisc is a special type of self-assembling membrane that mimics the cell membrane, allowing researchers to embed full-length receptors and study their function more easily.