Scientists discover learning and memory formation in model membranes

A decades-long collaboration between two Department of Energy Oak Ridge National Laboratory scientists is reshaping how we understand learning.

Their findings suggest that cellular membranes play a direct role in how memory and learning form in the brain. This work aims to advance materials science for neuromorphic, or low-power, brain-inspired, computing technologies and neurological disorders.

The discovery was made possible by ORNL's unique combination of expertise in soft matter science, world-leading neutron capabilities and co-located user facilities, which allowed researchers to investigate biological membranes in ways not previously possible.

"Science is a conversation," said John Katsaras, neutron scattering scientist at ORNL's Spallation Neutron Source, a Department of Energy Office of Science user facility. "Many years ago, Pat [Collier] and I wanted to see what would happen when we combined our scientific interests. He wanted to explore soft matter systems for neuromorphic computing [computing systems designed to mimic how the brain processes information], and I've studied the structure and dynamics of lipid membranes over the past 40 years. We are now applying decades of our soft matter experience to a problem neither one of us would have imagined pursuing five years ago."

Soft matter includes materials that readily change shape, such as membranes, gels and polymers. Although biological membranes vary in complexity, they all share a common foundation: a lipid bilayer, or double layer of molecules. Each lipid contains a hydrophilic (water-attracting) head and a hydrophobic (water-repelling) tail.

To study membrane properties under electrical stimulation, Katsaras and Collier used water droplets suspended in oil, known as a droplet interface bilayer. These early experiments showed unexpected electrical data, prompting them to shift their attention to membranes surrounding neurons, where many memory and learning processes occur.

When simple membranes behave like neural systems

"Our early measurements revealed stable changes in the membrane's electrical behavior - patterns typically associated with neural activity," said Collier, a cleanroom process engineer at ORNL's Center for Nanophase Materials Sciences, also a DOE Office of Science user facility. "Working with a broad group of collaborators, we developed new experimental approaches and observed results consistent with biological memory and learning occurring in these bilayers."

Scientists have long known that ion activity drives brain signaling. Katsaras and Collier have shown that lipid bilayers play an active role in regulating how these ions flow through membrane proteins.

"We've shown memristance and memcapacitance [electrical properties of devices with electrical resistance that depend on the history of applied voltage] taking place within the same membrane," Collier said. "In one region of a membrane, a lipid bilayer might rearrange to form a memory resistor, and in another region, it can behave as a memory capacitor. These properties could accelerate the development of new classes of soft materials capable of enhanced, highly versatile neural sensing and computing."

In upcoming experiments, the team plans to use neutron scattering and lithium to demonstrate how molecules within these membranes rearrange to increase or decrease the flow of potassium ions, like a faucet controlling the flow of water. By capturing these structural changes in unprecedented detail, neutron scattering can offer direct nondestructive, atomic-scale measurements of how lipid bilayers alter the environment surrounding membrane proteins.

In these experiments, they also plan to demonstrate how these lipid molecules interact with lithium, which is widely used to treat bipolar disorder and has been studied for potential neuroprotective effects in neurodegenerative diseases, including Alzheimer's disease. If successful, these interactions could bring new insights into the use of lithium in artificial synapses, or electronic components designed to mimic the connections between brain cells, and other neuromorphic computing technologies.

Membranes may help build memories

Drawing on the strengths of ORNL's co-located user facilities, Katsaras and Collier have worked closely with researchers across the laboratory, including experts at the Oak Ridge Leadership Computing Facility, host of Frontier, the world's first exascale supercomputer. Collaborations with national and international partners have further strengthened the effort, showing how multidisciplinary science can drive discoveries and innovation in materials science.

Over the last five years, Collier and Katsaras have assembled a growing body of evidence for their work. In 2022, they showed that lipid bilayers can mimic key features of long-term memory. More recently, they showed that electrical and mechanical cues can restructure bilayers in ways that support distinct, stable memory states, and they identified mechanisms that allow those states to persist.

In collaboration with Louisiana State University, the team also extended its findings to rotaxanes, tiny molecular machines that change shape under light and act as molecular switches. Experiments showed that these light-triggered changes can drive membranes to reorganize between memory and learning.

"This research highlights how ORNL's world-leading expertise in soft matter, advanced characterization and user facilities is enabling discoveries at the intersection of biology, materials science and computing," said Jon Taylor, associate laboratory director for Neutron Sciences at ORNL. "These findings support the lab's mission of translating fundamental science into technologies that address national priorities."

Read more about neutron scattering and membranes at ORNL here and here.

The research by Collier and Katsaras was partly supported by the Nonequilibrium and Emergent Transients in Advanced and Soft Materials award, sponsored by the Laboratory Directed Research and Development Program.

UT-Battelle manages ORNL for DOE's Office of Science, the single largest supporter of basic research in the physical sciences in the United States. The Office of Science is working to address some of the most pressing challenges of our time. For more information, visit energy.gov/science. - Sumner Brown Gibbs