Tip links are composed of filamentous structures, which connect the tips of stereocilia in adjacent rows within bundles by connecting the top of one hair cell to the side of the adjacent taller hair cell which ulitmately causes directional selectivity of transduction in hair bundles. Tip links are also important for mechanotransduction. 
Tip links are filaments made up of two cadherin molecules- protocadherin 15 and cadherin 23. These proteins are characterized by long extracellular domains that attach end-to-end via a calcium-dependent mechanism. The two proteins bind to form an overlapped, antiparallel heterodimer strong enough to resist the mechanical forces acting on the hair cell. This complex has been found to be weakened in the absence of calcium ions. .
Tip links are an essential element of mechanoelectirical transduction in sensory hair cells of the inner ear. Mechanoelectrical transduction is the conversion of mechanical stimuli from sound and head movements into electrochemical signal. Tip links are combined in the gating spring hypothesis of mechanotransduction in hair cells that describes tip links as tiny springs. Deflection of the hair bundle in the positive direction, towards the taller hairs, separates the tips to stretch a gating spring and pulling open the transduction channel. When the hair bundle is pushed in the opposite direction, towards the smaller hairs, the spring is compressed and the channels close. They also are involved in the force transmission across the bundle and the maintenance of the hair bundle structure.
Tip Links and Adaptation
Tips links have been implicated in the process of slow adaptation in hair cells. In the tip link adaptation hypothesis, myosin-1c motors attach to the actin filament within the stereocilia and the cadherins within the tip links. After continued and repeated stimulation, the myosin motor moves along the actin, thus changing the amount of tension in the tip links connecting adjacent stereocilia. Altering the tension of the tip links effectively closes the transduction channels, so that a larger stimulus is required to open the channels following this adaptation. This allows the hair cells to respond more strongly to changes in environmental stimuli, rather than continued background input.
Tip Link Destruction
The extracellular domains of the two cadherins that make up the tip links have been implicated in the pathology of deafness. Dysfunction of tip links caused by mutations of such tip link proteins have been found to cause hearing impairment in humans. Large mechanical stimulation (i.e. loud sounds) have been found to break the linkages between the cadherins of the tip links, causing deafness. Additionally, the removal of calcium has been found to indirectly weaken the bond between the cadherin molecules. Many mutations associated with deafness in humans and other animals affect the protocadherin 15 and cadherin 23 extracellular domains, most of which also affect calcium binding sites on the proteins.
- PMID 6436216 (PubMed)
- Sotomayer M, Weihofen WA, Gaudet R, Corey DP. Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Nature (2012) 492(7427):128-32.
- Template:A. Wayne Orr, Brian P. Helmke, Brett R. Blackman, Martin A. Schwartz, Mechanisms of Mechanotransduction, Developmental Cell, Volume 10, Issue 3, March 2006, Page 407, ISSN 1534-5807, 10.1016/j.devcel.2006.02.015.
- Template:Cite PMID
- Holt JR, Gillespie KH, Provance DW, Shah K, Shokat KM, Corey DP, Mercer JA, Gillespie PG. A Chemical-Genetic Strategy Implicates Myosin-1c in Adaptation by Hair Cells. Cell (2002) 108: 371-381.
- Template:Sakaguchi, Hirofumi, Joshua Tokita, Ulrich Müller, and Bechara Kachar. "Tip Links in Hair Cells: Molecular Composition and Role in Hearing Loss." Current Opinion in Otolaryngology & Head and Neck Surgery 17.5 (2009): 388-93. Print.
- ↑ Sotomayer M, Weihofen WA, Gaudet R, Corey DP. Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Nature (2012) 492(7427):128-32.