This special Physics department colloquium is scheduled for Thursday 4/30/15 at 4:00 pm in Room 135. Coffee, tea and cookies are served at 3:45 pm in the same room. Anyone is welcome.

Uncovering the nano-mechanics of giant muscle protein titin using a novel single molecule approach
Dr. Ionel Popa, Postdoctoral Research Scientist, Department of Biological Sciences, Columbia University, New York, NY

Current theories of muscle contraction propose that the power of stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscle tissue. Using a technique developed during my postdoctoral training based on a combination of Halo Tag covalent attachment and magnetic tweezers, we have discovered that titin Ig domains from the elastic I band region undergo unfolding/folding reactions at physiological forces of 6-8 pN. The spontaneous folding contraction can take place at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, a value larger than the mechanical energy delivered by the power stroke of a myosin motor. Based on hour-long recording of single multidomain proteins investigated under force-clamp condition, we have demonstrated a new approach of the construction of the free energy of a protein under force, which includes the physics of extending the polypeptide. The experimental and theoretical advances that I will present strongly suggest the need for the addition of a new force-generating element, titin, to the actomyosin theory of muscle contraction and provide a more realistic modeling for tissue elasticity. Fully deciphering how proteins operate in vivo under force will be a critical area of research as this may provide key insights into developing new theories for muscular dystrophy, cancer or misfolding diseases.