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Gladys Alexandre

Gatekeepers – Gladys Alexandre

by Laura Buenning

Cell membranes define biological cells.

They are the gatekeepers, says JDRD team leader Gladys Alexandre—the guardians that designate what’s in, what’s out, and what comes in and goes out of the cell.

In healthy cells, phospholipids and proteins form a fluid mosaic. The phospholipid molecules—with their water-friendly heads and oily, water-repellant tails (two each)—line up in a bilayer; their tails tucked between their heads to form a two-sided boundary. The membrane itself behaves like a two-dimensional fluid in which proteins and lipids are free to rotate and move laterally inside the structure. Within the membrane, the proteins fold themselves to generate energy, pass signals, or create selective openings that carry essential substances into and out of the cell.

alexandre_a-aksenovaSo, Alexandre says, maintaining fluidity is crucial to cell health. Organisms have evolved mechanisms to control membrane fluidity and viscosity, which changes as temperatures fluctuate, nutritional conditions vary, and the cells enter new stages in their growth cycle. Bacteria, for example, regulate fluidity by changing the length of fatty acid chains in the membrane: longer chains reduce fluidity; shorter lengths do the opposite.

Alexandre’s recent serendipitous discovery of a protein present in all known genomes—humans included—set the stage for her JDRD/LDRD partnership with Robert Standaert. Standaert’s team is developing techniques using neutrons to discover how biomembranes change and influence protein activity.

Alexandre and graduate students, Anastasia Aksenova, Jessica Gullett, and Tammoy Mukherjee chose Escherichia coli as a working model to discover if the newfound protein functions as a sensor and regulator of membrane fluidity, as some research suggests.

“To find out what a protein does you look at one that’s defective,” Alexandre says.

Preliminary research revealed two important results.

alexandre_mukherjee_gullettBy comparing “wild type” E. coli, witch has a normal copy of the new protein, with mutant E. coli, or those missing the protein altogether, they found no difference in the abundance or kinds of proteins present in the membrane, but a significant difference in distribution. While the proteins of wild type organisms were organized in discrete regions the same proteins in the mutants appeared to be distributed throughout the membrane.

“Where proteins gather is an important factor in cell function,” Alexandre says.

Furthermore, wherever the team isolated a mutant cell with a defective or missing protein they also found a change in the length of membrane lipids. Using dyes specific for testing membrane lipids of mutated and normal E. coli and a distant relative, Bacillus subtilis, they found that the differing fatty-acid chain lengths altered permeability to dyes and other compounds usually capable of crossing the membrane. Unaltered bacteria allowed far more dye through than their mutant counterparts.

“This suggests the new protein might help regulate fluidity in a way we haven’t identified before—as a receptor, or as something that responds to a signal to regulate lipid-making proteins, or as a catalyst for some activity,” Alexandre says.

“We don’t know, but this project will help us begin to find out.”

JDRD project:
Function of a universally conserved protein in regulating membrane fluidity
Gladys Alexandre, UT Biochemistry and Cellular and Molecular Biology Department

LDRD project:
New capabilities for neutron-based biomembrane research
Robert Standaert, ORNL Biosciences and Biology and Soft Matter divisions