2022-12-06 オークリッジ国立研究所(ORNL)
この成果は、人工細胞膜が長期増強(LTP)機能を持つことを示すもので、生物学的学習と記憶の特徴である。これは、タンパク質やその他の生体分子を含まない細胞膜が、何時間もLTPを持続させることができることを示す初めての証拠となる。また、記憶がコード化されるナノスケール構造も初めて確認された。
この研究で使われたナノスケールシステムは、油懸濁液の中に、2つのミクロンサイズの脂質でコーティングされた水滴を一緒にすることで人工膜を作り出している。2つの液滴の界面には、人間の脳の神経細胞のシナプスの細胞膜を模倣した脂質二重層が形成される。
ORNLの以前の研究では、この生体膜システムは電荷を蓄えることができるが、短時間しか蓄えることができないことが分かっていた。今回の研究では、LTPの存在は、このソフトマテリアルシステムをニューロモルフィックデバイスにどのように利用できるか、あるいは同様の機能を持つ固体デバイスを構築するためのモデルとしてどのように役立つかについて、新しい道が開かれることを意味している。
<関連情報>
- https://www.ornl.gov/news/biomembrane-research-findings-could-advance-understanding-computing-and-human-memory
- https://www.pnas.org/doi/10.1073/pnas.2212195119
リン脂質膜における長期増強の証拠 Evidence for long-term potentiation in phospholipid membranes
Haden L. Scott, Dima Bolmatov, Peter T. Podar, Zening Liu, Jacob J. Kinnun, Benjamin Doughty, Ralph Lydic, Robert L. Sacci, C. Patrick Collier and John Katsaras
Proceedings of the National Academy of Sciences Published:December 5, 2022
DOI:https://doi.org/10.1073/pnas.2212195119
Significance
Lipid bilayers have the potential to be developed into neuromorphic platforms which exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP), a feature associated with learning and memory. The results presented herein show that, even in the absence of peptides or proteins, lipid bilayers are capable of LTP emulating hippocampal LTP formation observed in mammals and birds. The data thus support the interpretation that the lipid bilayer provides a model for understanding the molecular basis of biological memory, as a therapeutic target for brain diseases that do not respond to drugs targeting proteins, and as a platform for artificial neural network developments and memcomputing using crossbar architectures of two-terminal passive circuit elements.
Abstract
Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating the brain’s efficiency and flexible cognitive capabilities. However, STP memory in lipid bilayers is volatile and cannot be stored or accessed over relevant periods of time, a key requirement for learning. Using droplet interface bilayers (DIBs) composed of lipids, water and hexadecane, and an electrical stimulation training protocol featuring repetitive sinusoidal voltage cycling, we show that DIBs displaying memcapacitive properties can also exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP) associated with capacitive energy storage in the phospholipid bilayer. The time scales for the physical changes associated with the LTP range between minutes and hours, and are substantially longer than previous STP studies, where stored energy dissipated after only a few seconds. STP behavior is the result of reversible changes in bilayer area and thickness. On the other hand, LTP is the result of additional molecular and structural changes to the zwitterionic lipid headgroups and the dielectric properties of the lipid bilayer that result from the buildup of an increasingly asymmetric charge distribution at the bilayer interfaces.
