Nanotechnology is the capability to build by controlling the arrangement of individual atoms and molecules. Such a technology would be founded on the ability to control, manipulate and investigate matter at the atomic scale. The invention of atomic force microscope (AFM) and the advances in micro-cantilever based scanning probe technology have significantly enhanced the experimental capability to probe and modify matter at the nanoscale. However, it is still severely limited in achieving the necessary bandwidth, sensitivity and resolution. To further the advances in this field an in-depth understanding of the nature and effects of the tip-sample interactions is imperative. A complementary approach involving theoretical investigations and experimental advances is best suited to overcome the current limitations of this technology.;This thesis investigates the atomistic phenomena associated with material modification at the tip-sample contact theoretically because such information is inaccessible to experimental observation. Molecular dynamics studies of nanoindentation of crystalline silicon and gold, representative of semiconductor and metallic substrates, shed light on the mechanics of plastic deformation and defect formation. Silicon undergoes a densification transformation to amorphous phase in the deformed region via the formation of interstitials. In gold a pyramidal defect structure is formed via a three step mechanism consisting of nucleation, glide and reaction of dislocations. This mechanism dictates the dependence of defect structure on the crystallography of the indented surface as observed in experimental studies performed by other researchers.;The experimental studies develop a new small amplitude non-contact AFM technique. In this frequency modulation method, changes in the cantilever's resonance induced by the tip-sample interactions are detected from its thermal noise response. By eliminating the need for positive feedback it enables maintaining an extremely small tip-sample separation for extended periods of time at room temperatures. Consequently, this technique is particularly suited for studying highly localized slowly evolving atomic or molecular scale phenomena at ambient temperatures. The experiments performed in ambient room conditions have achieved tip-sample separations less than 2 nm for time periods in excess of 30 min. At such small separations a narrowband signal at 250 Hz is imaged with a force sensitivity of 14 fN in a bandwidth of 0.4 Hz.