Multiple simultaneous interactions between receptors and ligands dictate the extracellular and intracellular activities of cells. The concept of programmable ligand display is generally used to study the interaction between ligands, displayed on surfaces at various densities, with receptors present on cell surfaces. Various strategies are discussed here to display ligands on surfaces to study their effect on cell behavior. Only very few strategies have been reported where this display combines precise control over density with lateral spacing of ligands on surfaces. In this review, selected examples of strategies to control ligand density and spacing and their implications for biological functions of cells are discussed.

The modulation of the hierarchical nucleated self-assembly of tri-b 3 -peptidesh as been studied. b 3 -Tyrosine provided ah andle to control the assembly process throughh ost-guest interactions with CB [7] and CB [8]. By varyingt he cavity size from CB [7] to CB [8] distinct phases of assembling tri-b 3 -peptides were arrested. Given the limited size of the CB [7] cavity,o nly one aromatic b 3 -tyrosine can be simultaneously hosted and, hence,C B [7] was primarily acting as an inhibitor of self-assembly.I ns trong contrast, the larger CB [8] can form at ernary complex with two aromatic amino acids and hence CB[8] wasa cting primarily as cross-linker of multiple fibersa nd promoting the formation of larger aggregates. General insights on modulating supramolecular assembly can lead to new ways to introduce functionality in supramolecular polymers.Our understanding of how synthetic peptides and other molecular systems self-assemble into helical structures has progressedi nr ecent decades towards ap rocesst hat mimics many aspects of nucleated assembly of proteins observed in nature. [1][2][3][4][5][6] As expected, the nucleated assembly of peptides requires distinct sequence motifsa nd their assembly can be modulated using conventional factors such as concentration, pH, time, and temperature. More interestingly,t he onset and regulation of peptideassembly can be activated by light or enzymatics witches. [7,8] In spite of these advances, the programmabilityo ft he hierarchical assembly of synthetic peptides and molecules into highero rderedf ibrillar structures remains challenging in contrast to for example, naturallyo ccurring b-sheets that hierarchically assemble into dimers, tetramers, protofibrils, and finally large fibrillar aggregates. [9] In particular, recent researchh as demonstrated that the addition of chirala uxiliaries or seed molecules can lead to either the exclusive formationo f metastable helical aggregates or allows control over fibrillar width and length, as shown in mechanistic assembly studies on aromatic disc-and rod-likem olecules. [10][11][12][13][14] Promisingresults have also been reported by Moore and co-workerst oc ontrol the final outcome of the nucleated assemblyo fa-peptides by the addition of polymer-peptide conjugates into discrete nanostructures. [15] Very recently,t he addition of macrocycles CB [7] and CB[8] assisted the assembly of functional dimeric and tetramericp roteins, protein wires, and cell clusters mediated by interactions of these macrocyclesw ith aromatic amino acids in proteins. [16][17][18][19][20][21] SpecificC B[7]-phenyla laninei nteractions were used by Kim and co-workerst oi nhibit a-peptide fibril formation [22] and by Urbacha nd co-workers to inhibit an onspecific protease. [18] a-Peptides composed of lesst han 15 amino acids generally do not adopt defined helicalc onformations,i na bsence of structuralc onstraints.I ns trong contrast, as urprising aspecto f b-peptides is that they adopt defined helical structures over very short sequences despitet h...

Chapter 2: Effects of variations in ligand density on cell signaling 2.1 Introduction 2.2 Surfaces with stochastic display of ligands 2.2.1 Ligand density variations in monolayers 2.2.2 Ligand density in bio-sensing 2.2.3 Activating the function of growth factor by spatially organizing binding ligands on SAMs 2.2.4 Ligand density variations in hydrogels 2.2.5 Ligand density variations on peptide amphiphiles 2.2.6 Ligand density variations in peptide nucleic acids 2.3 Surfaces with uniform arrangement of ligands 2.3.1 Ligand density variations on nanocorals 2.3.2 Spatial clustering of ligands 2.4 Conclusions and future perspectives 2.5 References Chapter 3: Employing the weakly binding aromatic amino acids for multivalent peptide complexation with β-CD printboards