The tiny spider makes
dragline silk fibers with unbeatable toughness,
all under the most innocuous conditions. Scientists have persistently
tried to emulate its natural silk spinning process using recombinant
proteins with a view toward creating a new wave of smart materials,
yet most efforts have fallen short of attaining the native fiber’s
excellent mechanical properties. One reason for these shortcomings
may be that artificial spider silk systems tend to be overly simplified
and may not sufficiently take into account the true complexity of
the underlying protein sequences and of the multidimensional aspects
of the natural self-assembly process that give rise to the hierarchically
structured fibers. Here, we discuss recent findings regarding the
material constituents of spider dragline silk, including novel spidroin
subtypes, nonspidroin proteins, and possible involvement of post-translational
modifications, which together suggest a complexity that transcends
the two-component MaSp1/MaSp2 system. We subsequently consider insights
into the spidroin domain functions, structures, and overall mechanisms
for the rapid transition from disordered soluble protein into a highly
organized fiber, including the possibility of viewing spider silk
self-assembly through a framework relevant to biomolecular condensates.
Finally, we consider the concept of “biomimetics” as
it applies to artificial spider silk production with a focus on key
practical aspects of design and evaluation that may hopefully inform
efforts to more closely reproduce the remarkable structure and function
of the native silk fiber using artificial methods.