Valves on the plant epidermis called stomata develop according to positional cues, which likely involve putative ligands (EPIDERMAL PATTERNING FACTORS [EPFs]) and putative receptors (ERECTA family receptor kinases and TOO MANY MOUTHS [TMM]) in Arabidopsis. Here we report the direct, robust, and saturable binding of bioactive EPF peptides to the ERECTA family. In contrast, TMM exhibits negligible binding to EPF1 but binding to EPF2. The ERECTA family forms receptor homomers in vivo. On the other hand, TMM associates with the ERECTA family but not with itself. While ERECTA family receptor kinases exhibit complex redundancy, blocking ERECTA and ERECTA-LIKE1 (ERL1) signaling confers specific insensitivity to EPF2 and EPF1, respectively. Our results place the ERECTA family as the primary receptors for EPFs with TMM as a signal modulator and establish EPF2–ERECTA and EPF1–ERL1 as ligand–receptor pairs specifying two steps of stomatal development: initiation and spacing divisions.

▪ Abstract Molecular biomimetics can be defined as mimicking function, synthesis, or structure of materials and systems at the molecular scale using biological pathways. Here, inorganic-binding polypeptides are used as molecular building blocks to control assembly and formation of functional inorganic and hybrid materials and systems for nano- and nanobiotechnology applications. These polypeptides are selected via phage or cell surface display technologies and modified by molecular biology to tailor their binding and multifunctionality properties. The potential of this approach in creating new materials systems with useful physical and biological properties is enormous. This mostly stems from molecular recognition and self-assembly characteristics of the polypeptides plus the added advantage of genetic manipulation of their composition and structure. In this review, we highlight the basic premises of molecular biomimetics, describe the approaches in selecting and engineering inorganic-binding polypeptides, and present examples of their utility as molecular linkers in current and future applications.