Molecular scale: regulation of self-assembly At the molecular scale, the spidroins are high molecular weight proteins with repetitive domains, driving their self-assembly in nanometer-scale structures 200 (Fig. ). The silk dope is itself highly complex, made of many components 178 . Each cell types secretes different composition and quantities of spidroins 159 , tuning the material properties at each layer 127 . The silk dope also contains a heterogeneous group of non-spidroin proteins with low molecular weight, named spider-silk constituting elements (SpiCE) . Peptides, lipids 202 , glycoproteins , and more 204 have also been reported in the silk dope. The hypothesized functions of the main components are: mechanical properties for spidroins; plasticity and support for SpiCE proteins; water balance, lubrication, and pliancy for glycoprotein coatings; and antibacterial protection and social signaling for outer-layer lipids . In most MA spidroins, crystalline regions are formed by polyA and polyGA domains, while glycine rich domains give an amorphous phase . The ratio and size of these domains affects the stiffness and extensibility of the fiber 207 . Spidroins are stored in the ampulla at high concentrations, up to 50% w/v 208 , higher than most artificial spinning . Spidroins self-assembly 178 can be described according to three models: micellar , liquid crystalline 209 , and liquid-liquid phase separation 210 (LLPS). Terminus domains (NT and CT) play a major role in this structure: NT dimerizes spidroins and transfers tensile forces, while CT contributes to the rapid, on demand polymerization of spidroins . Shear forces in the duct and drawdown effects further align spidroin nanoassemblies, stabilized in β-sheets structures . Once again, the spider silk gland showcases the intrinsic complexity of biological material composition and processing in vivo. To mimic silk self-assembly with recombinant expression and artificial spinning, the conditions should be greatly simplified. It is unclear if such reduction in complexity will be capable of producing the proper microstructure and versatile properties of biological materials, such as spider silk. Self-microfabrication, using tissue engineering, offers a complementary approach, aiming to grow material-producing organoids . Insights from spider development , at the single-cell resolution , are encouraging contributions toward this goal.