Point mutations alter the mechanical stability of immunoglobulin modules

Immunoglobulin-like modules are common components of proteins that play mec hanical roles in cells such as muscle elasticity and cell adhesion. Mutatio ns in these proteins may affect their mechanical stability and thus may com promise their function. Using single molecule atomic force microscopy (AFM) and protein engineering, we demonstrate that point mutations in two beta - strands of an immunoglobulin module in human cardiac titin alter the mechan ical stability of the protein, resulting in mechanical phenotypes. Our resu lts demonstrate a previously unrecognized class of phenotypes that may be c ommon in cell, adhesion and muscle proteins.