The self-assembly of molecular components into organized nanomaterials is a fundamental process observed in nature, crucial for various biological functions. Gaining a deepened understanding of the underlying self-assembly principles provides valuable insights into the molecular mechanisms of life. Additionally, such insights help the engineering of bio-inspired functional materials with emergent properties. However, studying self-assembly in biological systems is often difficult due to their inherent complexity. Therefore, simple and controllable model systems are needed to unravel these intricate processes. In this thesis, we design and fabricate synthetic DNA macromolecules inspired by natural self-assembling systems to determine the factors influencing the supramolecular self-assembly. By utilizing the programmability of DNA, we develop model systems that enable precise control and manipulation of self-assembly processes. This approach enhances our understanding of molecular self-assembly and facilitates the development of advanced nanomaterials with specific functions. Our research demonstrates the critical importance of monomer properties on the self-assembly process, particularly focusing on the interactions at the monomer-monomer interface (Chapter 2). Utilizing the unparalleled programmability and precision of DNA macromolecules, we explored how varying the structural characteristics and affinities of monomers impact their self-assembly. We introduced the concept of interface flexibility, finding that it plays a crucial role in the nucleation and growth mechanisms of supramolecular networks. Specifically, monomers with rigid interfaces formed large radial networks, whereas those with high flexibility lacked radial growth. Building on our findings, we continued to investigate the role of monomer-surface interactions in the self-assembly process (Chapter 3). By fine-tuning the interactions between DNA monomers and mica surfaces through adjustments in the ionic composition of the buffer solution, we optimized the conditions for effective self-assembly on surfaces. This led to significant improvements in the crystalline order of the assembled structures, demonstrating that surface interactions are vital for achieving high-quality crystalline networks. With a better understanding of self-assembly mechanisms, we aimed to regulate the assembly process more precisely (Chapter 4). We introduced a novel DNA tile designed to act as a seed for the nucleation of DNA monomers. This approach allowed for precise regulation of the assembly process by serving as an initiation point for the formation of larger crystals. Our findings show that these specially designed molecules can effectively govern and direct the self-assembly of supramolecular crystals, thus expanding the toolkit for precise assembly control. This thesis enlarges our current understanding of interface design principles that affect supramolecular self-assembly. By understanding and leveraging these principles, this research lays the groundwork for advancements in nanotechnology and materials science, contributing to the development of highly ordered and reproducible nanomaterials with tailored properties. Such materials have potential applications in electronic devices, energy storage, catalysis, tissue engineering, and biosensors, among many other potential uses.