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The effects of cytoskeleton orientation angle on strain transmission from a tissue to a cell and its internal cytoskeletons were investigated by using a model where a cell was integrated in a tissue that assumes a collagen gel construct. A cell with uni-directionally or randomly aligned cytoskeletons was embedded in a tissue, which was stretched to a strain of 0.1. When the initial orientation angle of the cytoskeleton was zero, which corresponded to the stretch direction of the tissue, cell strain was minimal and mean cytoskeletal strain was maximal. As the initial cytoskeleton orientation angle increased, mean cytoskeletal strain values decreased, while cell strain increased. Cell strain decreased at an initial cytoskeleton orientation angle of 60°. At this angle, the mean cytoskeletal strain value was nearly zero, which was absolutely minimal. Subsequent increases in the initial cytoskeleton orientation angle resulted in further decreases in cell and cytoskeletal strain. The present multi-scale model may help in achieving structural integration of the biomechanical organization and provide valuable information for understanding the mechanisms underlying cellular remodeling.