Neurexins are proteins involved in synapse signaling. Understanding molecular recognition in neurons requires a knowledge of neurexin elasticity at a single molecule level. We apply, for the first time, AFM force spectroscopy to reveal mechanical properties of rat neurexin 1 alpha (NRXN1 alpha). Spectra indicate a flexible hinge. The first event in the unfolding pathway is a change of neurexin shape accompanied by EGF-like E3 domain unfolding. This requires low forces on the order of 50 pN. The other LNS/LG domains require forces of 100 pN to be unfolded. The unfolding of core modules (L1-E1-L2) and (L3-E2-L4) is a two stage process. (C) 2011 Elsevier B.V. All rights reserved.