Abstract
Although it is known that stronger cell-extracellular matrix interactions will be developed as neurons mature, how such change influences their response against traumatic injury remains largely unknown. In this report, by transecting axons with a sharp atomic force microscope tip, we showed that the injury-induced retracting motion of axon can be temporarily arrested by tight NCAM (neural cell adhesion molecule) mediated adhesion patches, leading to a retraction curve decorated with sudden bursts. Interestingly, although the size of adhesion clusters (~0.5–1 μm) was found to be more or less the same in mature and immature neurons (after 7- and 3-days of culturing, respectively), the areal density of such clusters is three times higher in mature axons resulting in a much reduced retraction in response to injury. A physical model was also adopted to explain the observed retraction trajectories which suggested that apparent adhesion energy between axon and the substrate increases from ~0.12 to 0.39 mJ/m2 as neural cell matures, in good agreement with our experiments.
Highlights
Typical TIRFM images of the stained neural cell adhesion molecule (NCAM) at the axon-substrate interface of 3-day and 7-day cultured neurons are given in Figure 1B which clearly indicates that these molecules tend to aggregate into small clusters
Given that NCAM is a unique carrier of the polyanionic carbohydrate, polysialic acid (PSA) (Kiselyov et al, 2005; Dityatev and El-Husseini, 2006), allowing them to physically bind to the positively charged PLL on the coverslip, it is likely that strong adhesions are formed in these locations (Liu et al, 2020)
The size of NCAM clusters (∼0.5–1 μm) was found to be more or less the same in mature (7-day) and immature (3-day) neurons, the areal density of such clusters was three times higher in mature axons (Figure 1C) indicating that a much stronger adhesion with outside will be established as neuron matures
Summary
Strong attachment to the extracellular matrix (ECM) is critical for neural cells to execute biological duties such as information transmission (Fields and Stevens-Graham, 2002; Togashi et al, 2009), memory consolidation (Sandi, 2004; Washbourne et al, 2004), and nerve regeneration (Yu et al, 2008; Togashi et al, 2009; Eva and Fawcett, 2014; Nieuwenhuis et al, 2018). Periodic membrane skeleton (Zhong et al, 2014) will be developed in mature axons while such organized structure is often missing in immature ones. Adhesion proteins such as integrin were found to be widely distributed in the membrane of immature neural cells whereas their expression become relative low after neuron maturation (Eva and Fawcett, 2014; Nieuwenhuis et al, 2018).
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