Understanding the Melanocyte Distribution in Human Epidermis: an Agent-based Computational Model Approach

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jul 14

PMID 22792296

Citations 14

Authors

Josef Thingnes

Timothy J Lavelle

Eivind Hovig

Stig W Omholt

Affiliations

Soon will be listed here.

Abstract

The strikingly even color of human skin is maintained by the uniform distribution of melanocytes among keratinocytes in the basal layer of the human epidermis. In this work, we investigated three possible hypotheses on the mechanism by which the melanocytes and keratinocytes organize themselves to generate this pattern. We let the melanocyte migration be aided by (1) negative chemotaxis due to a substance produced by the melanocytes themselves, or (2) positive chemotaxis due to a substance produced by keratinocytes lacking direct physical contact with a melanocyte, or (3) positive chemotaxis due to a substance produced by keratinocytes in a distance-to-melanocytes dependent manner. The three hypotheses were implemented in an agent-based computational model of cellular interactions in the basal layer of the human epidermis. We found that they generate mutually exclusive predictions that can be tested by existing experimental protocols. This model forms a basis for further understanding of the communication between melanocytes and other skin cells in skin homeostasis.

Citing Articles

The Inhibitory Effect of Peptide Hydrolysate of Type I Collagen Derived from Pig Skin on Melanogenesis in B16F10 Melanoma Cells.

Zheng J, Xu D, Li T Biomolecules. 2025; 15(2).

PMID: 40001523 PMC: 11852596. DOI: 10.3390/biom15020220.

Melanin Biopolymers in Pharmacology and Medicine-Skin Pigmentation Disorders, Implications for Drug Action, Adverse Effects and Therapy.

Karkoszka M, Rok J, Wrzesniok D Pharmaceuticals (Basel). 2024; 17(4).

PMID: 38675481 PMC: 11054731. DOI: 10.3390/ph17040521.

Palmar reconstruction using full-thickness skin grafts from the groin and lateral malleolus regions: A comparison of long-term outcomes.

Choi J, Lee S, Kim K, Shin J, Hwang J, Lee S Medicine (Baltimore). 2023; 102(50):e36487.

PMID: 38115368 PMC: 10727646. DOI: 10.1097/MD.0000000000036487.

Current Status of Cell-Based Therapies for Vitiligo.

Domaszewska-Szostek A, Polak A, Slupecka-Ziemilska M, Krzyzanowska M, Puzianowska-Kuznicka M Int J Mol Sci. 2023; 24(4).

PMID: 36834766 PMC: 9964504. DOI: 10.3390/ijms24043357.

Reproduction of patterns in melanocytic proliferations by agent-based simulation and geometric modeling.

Schneckenreither G, Tschandl P, Rippinger C, Sinz C, Brunmeir D, Popper N PLoS Comput Biol. 2021; 17(2):e1008660.

PMID: 33539342 PMC: 7888658. DOI: 10.1371/journal.pcbi.1008660.

References

Madden K, Forman S, Elston D . Quantification of melanocytes in sun-damaged skin. J Am Acad Dermatol. 2011; 64(3):548-52. DOI: 10.1016/j.jaad.2010.05.021. View

Adra S, Sun T, MacNeil S, Holcombe M, Smallwood R . Development of a three dimensional multiscale computational model of the human epidermis. PLoS One. 2010; 5(1):e8511. PMC: 2799518. DOI: 10.1371/journal.pone.0008511. View

Scott G, Haake A . Keratinocytes regulate melanocyte number in human fetal and neonatal skin equivalents. J Invest Dermatol. 1991; 97(5):776-81. DOI: 10.1111/1523-1747.ep12486726. View

Le Poole I, van den Wijngaard R, Westerhof W, Dormans J, van den Berg F, Verkruisen R . Organotypic culture of human skin to study melanocyte migration. Pigment Cell Res. 1994; 7(1):33-43. DOI: 10.1111/j.1600-0749.1994.tb00016.x. View

Holbrook K, Underwood R, Vogel A, Gown A, KIMBALL H . The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45. Anat Embryol (Berl). 1989; 180(5):443-55. DOI: 10.1007/BF00305119. View

Ando H, Niki Y, Ito M, Akiyama K, Matsui M, Yarosh D . Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J Invest Dermatol. 2011; 132(4):1222-9. DOI: 10.1038/jid.2011.413. View

Slominski A, Paus R, Schadendorf D . Melanocytes as "sensory" and regulatory cells in the epidermis. J Theor Biol. 1993; 164(1):103-20. DOI: 10.1006/jtbi.1993.1142. View

Hachiya A, Sriwiriyanont P, Kaiho E, Kitahara T, Takema Y, Tsuboi R . An in vivo mouse model of human skin substitute containing spontaneously sorted melanocytes demonstrates physiological changes after UVB irradiation. J Invest Dermatol. 2005; 125(2):364-72. DOI: 10.1111/j.0022-202X.2005.23832.x. View

Mogilner A . Mathematics of cell motility: have we got its number?. J Math Biol. 2008; 58(1-2):105-34. PMC: 2862828. DOI: 10.1007/s00285-008-0182-2. View

10.

Walker D, Southgate J, Hill G, Holcombe M, Hose D, Wood S . The epitheliome: agent-based modelling of the social behaviour of cells. Biosystems. 2004; 76(1-3):89-100. DOI: 10.1016/j.biosystems.2004.05.025. View

11.

Jones P, Simons B, Watt F . Sic transit gloria: farewell to the epidermal transit amplifying cell?. Cell Stem Cell. 2008; 1(4):371-81. DOI: 10.1016/j.stem.2007.09.014. View

12.

Sun T, McMinn P, Coakley S, Holcombe M, Smallwood R, MacNeil S . An integrated systems biology approach to understanding the rules of keratinocyte colony formation. J R Soc Interface. 2007; 4(17):1077-92. PMC: 2396345. DOI: 10.1098/rsif.2007.0227. View

13.

Alaluf S, Barrett K, Blount M, Carter N . Ethnic variation in tyrosinase and TYRP1 expression in photoexposed and photoprotected human skin. Pigment Cell Res. 2003; 16(1):35-42. DOI: 10.1034/j.1600-0749.2003.00005.x. View

14.

Fitzpatrick T, Breathnach A . [THE EPIDERMAL MELANIN UNIT SYSTEM]. Dermatol Wochenschr. 1963; 147:481-9. View

15.

Rhoads D, Guan J . Analysis of directional cell migration on defined FN gradients: role of intracellular signaling molecules. Exp Cell Res. 2007; 313(18):3859-67. PMC: 2083117. DOI: 10.1016/j.yexcr.2007.06.005. View

16.

Hearing V . Regulating melanosome transfer: who's driving the bus?. Pigment Cell Res. 2007; 20(5):334-5. DOI: 10.1111/j.1600-0749.2007.00402.x. View

17.

Jensen U, Lowell S, Watt F . The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis. Development. 1999; 126(11):2409-18. DOI: 10.1242/dev.126.11.2409. View

18.

Alaluf S, Atkins D, Barrett K, Blount M, Carter N, Heath A . Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin. Pigment Cell Res. 2002; 15(2):112-8. DOI: 10.1034/j.1600-0749.2002.1o071.x. View

19.

Slominski A, Tobin D, Shibahara S, Wortsman J . Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004; 84(4):1155-228. DOI: 10.1152/physrev.00044.2003. View

20.

Tadokoro T, Yamaguchi Y, Batzer J, Coelho S, Zmudzka B, Miller S . Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Invest Dermatol. 2005; 124(6):1326-32. DOI: 10.1111/j.0022-202X.2005.23760.x. View