How the molecular structure of the structural, extracellular matrix protein collagen correlates with its mechanical
properties at different hierarchical structural levels is not known. We demonstrate the utility of optical tweezers to probe
collagen’s mechanical response throughout its assembly hierarchy, from single molecule force-extension measurements
through microrheology measurements on solutions of collagen molecules, collagen fibrillar gels and gelatin. These
experiments enable the determination of collagen’s flexibility, mechanics, and timescales and strengths of interaction at
different levels of hierarchy, information critical to developing models of how collagen’s physiological function and
stability are influenced by its chemical composition. By investigating how the viscoelastic properties of collagen are
affected by the presence of telopeptides, protein domains that strongly influence fibril formation, we demonstrate that these play a role in conferring transient elasticity to collagen solutions.
The mechanical response of biological molecules at the microscopic level contributes significantly to their function.
Optical tweezers are instruments that enable scientists to study mechanical properties at microscopic levels. They are
based on a highly focused laser beam that creates a trap for microscopic objects such as dielectric spheres, viruses,
bacteria, living cells and organelles, and then manipulates them by applying forces in the picoNewton range (a range that
is biologically relevant). In this work, mechanical properties of single collagen molecules are studied using optical
tweezers. We discuss the challenges of stretching single collagen proteins, whose length is much less than the size of the
microspheres used as manipulation handles, and show how instrumental design and biochemistry can be used to
overcome these challenges.