A Mechanistic Classification for Axon Membrane fusion by Chemical Fusogens
Salma A Abdou, BA1; Peter W Henderson, MD MBA2
1New York University School of Medicine, New York, NY; 2Icahn School of Medicine at Mount Sinai, New York, NY
Introduction Certain chemical agents, collectively known as “fusogens,” have been shown to induce membrane fusion, and this technology has recently been shown to be effective in axon membrane fusion after nerve injury when combined with epineurial repair. While the end result (phospholipid membrane fusion) is the same, each agent’s structure and function is different. The goal of this project was to develop the first axon fusion mechanistic classification system for fusogens.
Materials & Methods A literature review was undertaken to identify the most commonly reported agents in the literature to achieve cell fusion in protoplast, animal, or human models. Seven such fusogens were identified: polyethylene glycol (PEG), chitosan, dextran sulfate, n-nonyl bromide, calcium, sodium nitrate and H-alpha-7. The chemical structure, mechanism, and clinical application to date for each one was analyzed and compared.
Results Adapted from an earlier description by Sowers in generalized cell fusion, fusogens can achieve axon membrane fusion by one of two general mechanisms: by bringing the two cut ends of each axon into extremely close apposition which allows the inherent fluidity of the phospholipid membrane to lead to rearrangement and ultimately fusion, or else by modifying the axon membrane surface charges in order to thereby diminish repellent forces. These mechanisms can be considered “cell aggregation” and “membrane modification,” respectively (Figure). Importantly, these two mechanisms are not mutually exclusive; in fact, the most extensively studied fusogen, PEG, is thought to function via both mechanisms.
Conclusions Fusogens can be rationally grouped into two mechanistic categories Ė cell aggregators and membrane modifiers. We adapted this classification system in the setting of axonal membrane fusion, and suggest that utilizing both mechanisms (either by a combination of two fusogens that function by different mechanisms, or by a single fusogen that functions by both mechanisms such as PEG) can contribute to even better outcomes in peripheral nerve repair, and warrants ongoing investigation.
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