A node means the dihedral is lower than 90°, and an ideal node should have a dihedral close to 0°. We found the force transduction is inhibited and meets resistance at "node", causing a severe distortion of the structure and increasing of energy, therefore making a large stress at the node, which finally leads to a bond cleavage (see Figure for more details). Conventional mechanophores either have a highly strained small ring (e.g., cyclopropane, cyclobutane) or a chemically weak bond (e.g., O-O bond, S-S bond). However, our guideline suggests these are sufficiency rather than necessity. Molecules with a "node" conformation (i.e., a small dihedral angle) should be reactive under tensile force to form mechanoradicals. To generate such a "node" conformation, a bond that cannot rotate freely is required.