Magnetic tweezers have limited application on mechanical stability of proteins because accurate force measurement has been difficult for short tethers. Here, we report a novel method that allows magnetic tweezers to stretch short bio-molecules with accurate force calibration over wide range up to ~ 100 pN.  We apply this method to study the mechanical stability of protein Filamin A.
Filamin A cross-links actin fiber and binds with many transmembrane and cellular signaling proteins.  By using magnetic tweezers, it was found that domains 16-23 can response to force smaller than 10 pN, while domains 1-8 needs force bigger than 20 pN to be unfolded.  As some structures in domains 16-23 can be unfolded by forces smaller than 10 pN, it indicates that the auto-inhibited binding site in segment of domains 16-23 can be exposed by physiological relevant forces.  The possible force sensor function of Filamin A is supported by the experiment.