Chain Sliding versus β-Sheet Formation upon Shearing Single α-Helical Coiled Coils

Area of Science:

• Biomaterials Science
• Structural Biology
• Computational Chemistry

Background:

• Coiled coils (CCs) are crucial protein structures that dictate the mechanical properties of biological materials.
• These materials can undergo a force-induced transition from alpha-helices to beta-sheets (αβT), enhancing their strength.
• Previous simulations suggest this αβT is dependent on CC length and pulling speed.

Purpose of the Study:

• To investigate if de novo designed CCs can replicate the force-induced αβT observed in natural CCs.
• To determine the mechanical response and rupture forces of synthetic CCs with varying lengths (four to seven heptads).
• To explore the influence of pulling speed on the αβT phenomenon in CCs.

Main Methods:

• Utilized de novo designed coiled coils with lengths ranging from four to seven heptads.
• Employed single-molecule force spectroscopy to mechanically load CCs in shear geometry.
• Conducted molecular dynamics simulations at different pulling speeds (0.01 nm/ns and 0.001 nm/ns).

Main Results:

• Simulations at high pulling speeds (0.01 nm/ns) induced β-sheet formation in five- and six-heptad CCs, increasing mechanical strength.
• The αβT transition was less likely at lower pulling speeds (0.001 nm/ns) and not observed in force spectroscopy experiments.
• In shear geometry, β-sheet formation competed with interchain sliding, limiting the transition.

Conclusions:

• Synthetic coiled coils can be designed to exhibit force-induced transitions, mimicking natural biomaterials.
• The αβT phenomenon in CCs is highly dependent on loading conditions, including pulling speed and geometry.
• Efficient β-sheet formation requires specific loading conditions that prevent interchain sliding, such as tensile geometries or higher-order assemblies.