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The physical imperative in circadian rhythm: a cytoskeleton-related physically resettable clock mechanism hypothesis.

Organisms maintaining circadian rhythmicity are responding to physical constraint of a 24-hour cycle. Time-cue sensing is fundamental to the clock existence, and entrainment of circadian rhythm is indeed accessible to a wide variety of geophysical stimuli. Light-dark and temperature changes are the main time-cues. Additional physical forces such as barometric pressure, electrostatic and electromagnetic fields and gravity force, display a daily cyclic behavior and can function as secondary time-cues. A conceptual framework that contains explanations to all circadian properties including cell autonomous, environmental responsiveness and self-sustained character, is still lacking. It is argued that clock responsiveness to external cues is central to the cellular clock mechanism, and therefore, the nature of the time-cues and the pathways that enable the cell to respond to physical stimuli are of central importance. A role for cytoskeleton in clock entrainment mechanism is suggested in light of cytoskeleton's major involvement in cellular mechanotransduction.