title: 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.
authors: R&D Center, AmorePacific Corporation, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea.
authors: Hyunjung
authors: H
authors: Choi
authors: Mina
authors: M
authors: Kim
authors: Song Ih
authors: SI
authors: Ahn
authors: Eun-Gyung
authors: EG
authors: Cho
authors: Tae Ryong
authors: TR
authors: Lee
authors: Jennifer H
authors: JH
authors: Shin
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003712:Dendrites; D004129:Dimethylpolysiloxanes; D004548:Elasticity; D015870:Gene Expression; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020460:Melanosomes / Q000502:physiology; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012880:Skin Pigmentation / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology*; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D004129:Dimethylpolysiloxanes; D039503:Integrin alpha6; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D058951:gp100 Melanoma Antigen; C013830:baysilon; D014442:Monophenol Monooxygenase
keywords: mechanical stiffness; melanogenesis; melanoma; skin pigmentation