Soluble laminin polymers enhance axon growth of primary neurons in vitro

A substrate of laminin polymers formed at pH 4 (acidic pH-induced laminin; aLam) promotes neurite growth of embryonic rat cortical neurons better than a substrate of similar but structurally different laminin polymers formed at neutral pH (neutral pH-induced laminin; nLam). We investigated the effects of these laminin polymers, used as soluble supplements, on neurite growth of cultured adult rat primary dorsal root ganglion neurons. When added to the culture medium, aLam was found to promote neurite growth about twofold better than nLam. Immunoblocking experiments revealed that aLam elicited neurite growth to a similar extent through the α1 or α3 integrin subunit, while nLam required the availability of the α1 integrin subunit to elicit neurite growth. With aLam, but not nLam, immunoblocking of the α1 or α3 subunit resulted in an increase in the protein level of the alternative subunit. The presence of a mature focal adhesion complex, which is associated with neurite growth, was elevated in neurons in the presence of aLam relative to nLam or culture medium. Our data indicated that the two types of laminin polymers promote neurite growth of adult rat primary sensory neurons to a different degree, likely through different ligand-receptor interactions. These findings support the potential of soluble laminin polymers as injectable therapeutics for eliciting axon growth after nervous system injury. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2372-2381, 2018.