Efim Liberman (1925-2011) introduced in 1972 the idea of natural computation realized internally by living systems. He considered the physical principles employed by living systems as essential constraints that limit the computational process occurring in the course of adaptation, morphogenesis, and neural activity. The most general limits determined by the physical fundamental constants are universal for all nature. However, the more specific constraints are intrinsic to each biological system and can be overcome in the course of the evolutionary process. We discuss the roles of biological macromolecules, particularly the cytoskeleton, in shaping the actualization patterns formed in the internal measurement process occurring in living systems. Cytoskeletal rearrangements determine cellular, morphogenetic, and perceptive transformations in living systems and participate in the combinatorial genetic events that lead to evolutionary transformations. The operation of neurons is based on the transmission of signals via the cytoskeleton, where the digital output is generated that can be decoded through a reflexive action of the perceiving agent. It is concluded that the principles of natural computation formulated by Liberman represent the most fundamental feature of living beings and form the basis for the general theory of biological systems, with essential consequences for understanding metabolic closure, morphogenesis, evolution, and consciousness.