The surface modification of biomaterials with matrikines for tissue engineering application is one of the recent approaches to improve their biocompatibility. In an earlier study, a peptide containing 21 amino acid isolated from bovine tendon collagen was shown to promote good cell adhesion in HeLa cell, and a smaller region in the peptide was identified using bioinformatics tool to mediate cell-peptide interaction. Hence, the present study was undertaken to validate the cell adhesion property of the smaller region of the peptide and elucidate probable peptide-cell interaction pathway. Cell adhesion and proliferation properties of the peptide were studied on cells cultured on surfaces coated with varying concentrations of peptide. Expression of focal adhesion related proteins like paxillin and pFAK Tyr397 was confirmed by immunoblotting and immunofluorescence microscopy respectively. The anti-pFAK Tyr 397 stained confocal micrographs and mRNA transcription levels of Cdc42 and Rho further confirmed peptide mediated cell spreading. The change in the expression levels of integrin α1 and β1 indicates an integrin mediated cell–peptide interaction for cell survival and proliferation. Integrin mediated adhesion was further confirmed by anti-integrin blocking assay. The modulation of ECM components by the peptide was assessed by expression of COL1A1, TIMP mRNA levels and gelatin zymography for MMPs. The results of the study confirm the role of the small region of the larger collagen peptide in cell adhesion and proliferation and hint at the possible use of such small peptides as biocompatible surface modifiers for tissue scaffolds. © 2019 Elsevier Inc.