As a physical barrier of cells, the cell membrane plays a vital role in cell communications and signaling. Engineering cell membranes have attracted a great amount of attention in the field of biosensing, tissue engineering, and cell therapy, etc. Recently, synthetics DNAs have attracted considerable attention to remodel and functionalize live cell membranes. In particular, a type of amphiphilic lipid-DNA conjugate has been rationally designed and synthesized for this purpose. These conjugates have enabled a rapid, straightforward, and efficient cell membrane modification due to the hydrophobic-hydrophobic interaction between lipid moiety and lipid bilayer. Taking advantage of the highly precise and programmable self-assembly of DNAs, lipid-DNA conjugates have been used for membrane bioanalysis, therapeutics, building artificial membrane structures, and regulating cell–surface and cell–cell interactions. In this thesis, I would mainly focus on how we have applied lipid-DNA conjugates for selective modification of cell membranes and for the investigation of intercellular mechanotransduction. First, we described the development of a simple, fast, and highly efficient system to engineer bacterial membranes with designer DNA molecules by using lipid-DNA conjugates. We have constructed a small library of synthetic lipid-DNA conjugates and characterized their membrane insertion properties on various Gram-negative and Gram-positive bacteria. Simply after incubation, these lipid-DNA conjugates can be rapidly and efficiently inserted onto target bacterial membranes. Based on the membrane selectivity of these conjugates, we have further demonstrated their applications in differentiating bacterial strains and potentially in pathogen detection. These lipid-DNA conjugates are promising tools to facilitate the possibly broad usage of DNA nanotechnology for bacterial membrane analysis, functionalization, and therapy. Secondly, we applied these lipid-DNA conjugates for the development of molecular tension probes to visualize tensile forces between cells. Mechanical forces are important stimuli in signaling pathways and regulate cell proliferation, adhesion, and differentiation, etc. We designed several ratiometric DNA tension probes to study the roles of intercellular tensile force during Notch1 activation. Our data indicated that the mechanical force Notch1 receptor exerts on its different ligands were quite different. In addition, our data indicated that the force could be generated when ligand endocytosis was not available, indicating that the force could be induced both by Notch ligands and receptors. Finally, we reported the first-time usage of DNA molecular tension probes in visualizing and detecting mechanical forces within 3D spheroids and embryoid bodies (EBs). By varying the concentrations of these DNA probes and their incubation time, we have first ix characterized the kinetics and efficiency of probe penetration and loading onto tumor spheroids and stem cell EBs of different sizes. After optimization, we have further imaged and measured E-cadherin-mediated forces in these 3D spheroids and EBs for the first time. Our results indicated that these DNA-based molecular tension probes can be used to study the spatiotemporal distributions of target mechanotransduction processes. Besides, these powerful imaging tools may be potentially applied to fill the gap between ongoing research of biomechanics in 2D systems and that in real 3D cell complexes. In sum, we described the applications of lipid-DNA conjugates on efficient and targeted membrane modification and intercellular tensile force visualization in this dissertation. The high efficiency and selectivity of lipid-DNA conjugates on bacterial membrane may allow a broad applications of DNA nanotechnology on prokaryotic cells, such as cell surface engineering, manipulation of cell-cell communications, and drug delivery, etc. Besides, the selectivity of lipid-DNA conjugates on bacterial membranes could provide some insights on achieving targeted modification on cell membranes, which is a current challenge in the field. On the other hand, the studies of intercellular mechanical forces in 2D and 3D cell models indicated the versatility of molecular DNA tension probes, which might be feasible to investigate mechanotransductions in real tissue with further optimization. The investigation of intercellular force during Notch activation may shed some light on revealing the regulation mechanisms or patterns of Notch signaling pathways. In addition, the direct visualization and flexibility of molecular DNA tension probes would allow the imaging of a great amount of mechano-sensitive ligand-receptor interaction in molecular level.