Endothelialization is a key phenomenon required to maintain the patency in tissue engineered vascular grafts (TEVGs). Different approaches have been used to functionalize the surface of the lumen of TEVGs to induce Endothelial cells (ECs) adhesion and spreading. A promising strategy to promote integrin mediated signal transduction is to functionalize the TEGVs surface with peptide motifs. This approach is known to induce ECs adhesion, spreading, and tubular formation. However, surface functionalization is challenging given the availability of functional groups and the peptide - cell affinity under hemodynamic flow conditions. For that reason, herein we propose a chemo-mechanical model to study the optimal ligand distribution to improve cell adhesion and spreading under laminar flow. A computational multiphysics model was performed aided by the software COMSOL Multiphysics 5.5. The coupling of the Chemistry and Surface Reaction modules was carried out in order to predict the interaction between EC Integrins and Surface Functionalized peptides on the TEVG intima layer. The attachment and spreading of a single unit EC submitted to laminar flow and its influence on EC matrix interface interaction was evaluated with a Fluid-Structure Interaction model. A positive correlation between the concentration of Surface Functionalized peptides and ECs attachment and spreading time was found until equilibrium. Maximum cell spreading occurred under high binding integrin-surface affinity and physiological baseline low flow velocities. The proposed model elucidated the role of binding forces and flow velocities over cell spreading and detachment depending on ligand concentration. This model can contribute in optimizing surface functionalization of TEVGs for promoting successful endothelialization.