Regulation of pigmentation by substrate elasticity in normal human melanocytes and melanotic MNT1 human melanoma cells

Abstract

The elasticity of the cellular microenvironment is a key regulator of cellular physiology in many cell types. To investigate the effects of substrate stiffness on the pigmentation process, we cultured normal human melanocytes (NHM) and MNT1 melanoma cells on laminin-coated polydimethylsiloxane (PDMS) substrates of different stiffness. The dendricity of NHM and MNT1 cells was reduced as the substrate stiffness decreased, and the degree of melanosome transfer from NHM or MNT1 cells to normal human keratinocytes was decreased on softer substrates with the reduced dendricity. Gene and protein expressions of MITF, tyrosinase, TRP2, and gp100/PMEL17 exhibited a consistent decreasing trend with the decreasing stiffness. Because the stiffness sensing is mediated by focal adhesion complex through integrin receptors, we checked laminin specific integrin alpha 6 and p-FAK for MNT1 cells to observe that the substrate adhesion was weakened as the substrate stiffness decreased. Weaker adhesion on a softer substrate was accompanied by dynamic shape changes in MNT1 cells with higher speed and larger scattering. Dendritic MNT1 cells cultured on a stiffer substrate exhibited lower migration with smaller root mean squared displacement. These results demonstrate the possibility that skin pigmentation can be influenced by mechanical properties of the cellular microenvironment and can increase when the skin becomes stiff.

Loss of cell invasiveness through PKC‐mediated syndecan‐1 downregulation in melanoma cells under anchorage independency

“…It was known the SDC2 expression was associated with melanogenesis. Several genes, such TYR , TYRP1 , MITF and MC1R , were associated with melanin synthesis , and this process was modulated by elasticity of microenvironment , including proteoglycan expression . Overexpression of melanocortin 1 receptor (MC1R) enhances SDC2 expression through deactivation of p38 MAPK and promoted cell migration .…”

Melanoma in the Eyes of Mechanobiology

“…The dendrites allow the transfer of the melanin to keratinocytes, which will be transferred to the stratum corneum layer of the epidermis. of elastic properties according to Choi et al (2014). The authors studied the effect of substrates with different stiffness on the pigmentation, using normal human melanocytes (NHM) and melanoma cells (MNT1) cultured on polydimethylsiloxane (PDMS) coated with laminin.…”

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model

“…Cells without cilia enhance Wnt signaling, whereas cells with multiple cilia reduce its responses [14]. The pigmentation of human skin is influenced by external stimuli such as ultraviolet radiation (UVR), microenvironmental stiffness, inflammation, and hormones [15,16]. The pigmentation of human skin is regulated by a complex process involving the synthesis and distribution of melanin.…”