Doing What Spiders Cannot—A Road Map to Supreme Artificial Silk Fibers

[Image: see text] Fabricating artificial spider silk fibers in bulk scale has been a major goal in materials science for centuries. Two main routes have emerged for making such fibers. One method uses biomimetics in which the spider silk proteins (spidroins) are produced under nativelike conditions and then spun into fibers in a process that captures the natural, complex molecular mechanisms. However, these fibers do not yet match the mechanical properties of native silk fibers, potentially due to the small size of the designed spidroin used. The second route builds on biotechnological progress that enables production of large spidroins that can be spun into fibers by using organic solvents. With this approach, fibers that equal the native material in terms of mechanical properties can be manufactured, but the yields are too low for economically sustainable production. Hence, the need for new ideas is urgent. Herein, we introduce a structural-biology-based approach for engineering artificial spidroins that circumvents the laws with which spidroins, being secretory proteins, have to comply in order to avoid membrane insertion and provide a road map to the production of biomimetic silk fibers with improved mechanical properties.