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A Biophysical Model for the Staircase Geometry of Stereocilia.

Orly G, Manor U, Gov NS - PLoS ONE (2015)

Bottom Line: While recent genetic studies have provided a significant increase in information on the multitude of stereocilia protein components, there is currently no model that integrates the basic physical forces and biochemical processes necessary to explain the emergence of the SCG.We demonstrate that polarization of the cell's apical surface, due to the lateral polarization of the entire epithelial layer, plays a key role in promoting SCG formation.Furthermore, our model explains many distinct features of the manifestations of SCG in different species and in the presence of various deafness-associated mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Physics, The Weizmann Institute of Science, P.O.B. 26, Rehovot, Israel 76100.

ABSTRACT
Cochlear hair cell bundles, made up of 10s to 100s of individual stereocilia, are essential for hearing, and even relatively minor structural changes, due to mutations or injuries, can result in total deafness. Consistent with its specialized role, the staircase geometry (SCG) of hair cell bundles presents one of the most striking, intricate, and precise organizations of actin-based cellular shapes. Composed of rows of actin-filled stereocilia with increasing lengths, the hair cell's staircase-shaped bundle is formed from a progenitor field of smaller, thinner, and uniformly spaced microvilli with relatively invariant lengths. While recent genetic studies have provided a significant increase in information on the multitude of stereocilia protein components, there is currently no model that integrates the basic physical forces and biochemical processes necessary to explain the emergence of the SCG. We propose such a model derived from the biophysical and biochemical characteristics of actin-based protrusions. We demonstrate that polarization of the cell's apical surface, due to the lateral polarization of the entire epithelial layer, plays a key role in promoting SCG formation. Furthermore, our model explains many distinct features of the manifestations of SCG in different species and in the presence of various deafness-associated mutations.

No MeSH data available.


Related in: MedlinePlus

(a) Calculated heights and radii using the theoretical model, with the St.St solutions indicated by the red circles. Here we take a linear spatial gradient in γc, and a polymerization rates A(h) that increases sharply with height (as shown in the inset). We get a staircase structure (b) a large jump in height for the first (tallest) row. This row may be either thinner or thicker than the other rows [2], as indicated by the solid green line (a) and dark blue shade in (b) and dashed green line (a) and the light blue shade (b) respectively. This result from the model compares well with the stereocilia bundle of the mammalian inner-hair cell (c) [26] (Sekerková G et al. (2011) Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet, 7(3), e1002032-e1002032).
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pone.0127926.g004: (a) Calculated heights and radii using the theoretical model, with the St.St solutions indicated by the red circles. Here we take a linear spatial gradient in γc, and a polymerization rates A(h) that increases sharply with height (as shown in the inset). We get a staircase structure (b) a large jump in height for the first (tallest) row. This row may be either thinner or thicker than the other rows [2], as indicated by the solid green line (a) and dark blue shade in (b) and dashed green line (a) and the light blue shade (b) respectively. This result from the model compares well with the stereocilia bundle of the mammalian inner-hair cell (c) [26] (Sekerková G et al. (2011) Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet, 7(3), e1002032-e1002032).

Mentions: When there is a sharp dependence in A(h), as shown in Fig 4, the first row can be significantly taller than the second row, as is observed in many mammalian inner hair cells [10, 22, 26, 29]. This tallest row may be either thinner or thicker than the second row, depending on the height dependence of the actin polymerization and the flux of the components that compose the tip-complex [2]: Rtip can also increase with the increase in h, depending on the regime of the control parameters (see [2] for more details). We note that additional factors could also contribute to the large jump in its height. For example, the existence of proteins associated with the tip-link in all but the first row can affect the polymerization directly through capping activity [15], or indirectly through the difference in Ca2+ concentration [30], and both can diminish the heights of the stereocilia except for the first row.


A Biophysical Model for the Staircase Geometry of Stereocilia.

Orly G, Manor U, Gov NS - PLoS ONE (2015)

(a) Calculated heights and radii using the theoretical model, with the St.St solutions indicated by the red circles. Here we take a linear spatial gradient in γc, and a polymerization rates A(h) that increases sharply with height (as shown in the inset). We get a staircase structure (b) a large jump in height for the first (tallest) row. This row may be either thinner or thicker than the other rows [2], as indicated by the solid green line (a) and dark blue shade in (b) and dashed green line (a) and the light blue shade (b) respectively. This result from the model compares well with the stereocilia bundle of the mammalian inner-hair cell (c) [26] (Sekerková G et al. (2011) Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet, 7(3), e1002032-e1002032).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514777&req=5

pone.0127926.g004: (a) Calculated heights and radii using the theoretical model, with the St.St solutions indicated by the red circles. Here we take a linear spatial gradient in γc, and a polymerization rates A(h) that increases sharply with height (as shown in the inset). We get a staircase structure (b) a large jump in height for the first (tallest) row. This row may be either thinner or thicker than the other rows [2], as indicated by the solid green line (a) and dark blue shade in (b) and dashed green line (a) and the light blue shade (b) respectively. This result from the model compares well with the stereocilia bundle of the mammalian inner-hair cell (c) [26] (Sekerková G et al. (2011) Roles of the espin actin-bundling proteins in the morphogenesis and stabilization of hair cell stereocilia revealed in CBA/CaJ congenic jerker mice. PLoS Genet, 7(3), e1002032-e1002032).
Mentions: When there is a sharp dependence in A(h), as shown in Fig 4, the first row can be significantly taller than the second row, as is observed in many mammalian inner hair cells [10, 22, 26, 29]. This tallest row may be either thinner or thicker than the second row, depending on the height dependence of the actin polymerization and the flux of the components that compose the tip-complex [2]: Rtip can also increase with the increase in h, depending on the regime of the control parameters (see [2] for more details). We note that additional factors could also contribute to the large jump in its height. For example, the existence of proteins associated with the tip-link in all but the first row can affect the polymerization directly through capping activity [15], or indirectly through the difference in Ca2+ concentration [30], and both can diminish the heights of the stereocilia except for the first row.

Bottom Line: While recent genetic studies have provided a significant increase in information on the multitude of stereocilia protein components, there is currently no model that integrates the basic physical forces and biochemical processes necessary to explain the emergence of the SCG.We demonstrate that polarization of the cell's apical surface, due to the lateral polarization of the entire epithelial layer, plays a key role in promoting SCG formation.Furthermore, our model explains many distinct features of the manifestations of SCG in different species and in the presence of various deafness-associated mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Physics, The Weizmann Institute of Science, P.O.B. 26, Rehovot, Israel 76100.

ABSTRACT
Cochlear hair cell bundles, made up of 10s to 100s of individual stereocilia, are essential for hearing, and even relatively minor structural changes, due to mutations or injuries, can result in total deafness. Consistent with its specialized role, the staircase geometry (SCG) of hair cell bundles presents one of the most striking, intricate, and precise organizations of actin-based cellular shapes. Composed of rows of actin-filled stereocilia with increasing lengths, the hair cell's staircase-shaped bundle is formed from a progenitor field of smaller, thinner, and uniformly spaced microvilli with relatively invariant lengths. While recent genetic studies have provided a significant increase in information on the multitude of stereocilia protein components, there is currently no model that integrates the basic physical forces and biochemical processes necessary to explain the emergence of the SCG. We propose such a model derived from the biophysical and biochemical characteristics of actin-based protrusions. We demonstrate that polarization of the cell's apical surface, due to the lateral polarization of the entire epithelial layer, plays a key role in promoting SCG formation. Furthermore, our model explains many distinct features of the manifestations of SCG in different species and in the presence of various deafness-associated mutations.

No MeSH data available.


Related in: MedlinePlus