Cell shape normalization, dendrite orientation, and melanin production of normal and genetically altered (haploinsufficient NF1)-melanocytes by microstructured substrate interactions

被引:43
作者
Jungbauer, S
Kemkemer, R
Gruler, H
Kaufmann, D
Spatz, JP
机构
[1] Univ Heidelberg, Inst Phys Chem, D-69120 Heidelberg, Germany
[2] Univ Ulm, Dept Biophys, D-89081 Ulm, Germany
[3] Univ Ulm, Dept Human Genet, D-89081 Ulm, Germany
关键词
D O I
10.1002/cphc.200300868
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Little is known about how functional regulation failure in genetically altered cells is influenced by topographical confinement of cells, a situation often present in tissues in vivo. We used cultured melanocytes derived from human skin samples as a model system for such investigations. Normal melanocytes have a very well defined shape consisting of a cell body and two dendrites arranged 180degrees relative to each other. In contrast, neurofibromin 1-melanocytes (NF1-melanocytes) have up to a 50% reduction of neurofibromin 1, which results in an altered morphology that can be easily measured. NF1-melanocytes deviate from the defined structure of normal melanocytes by forming more than two dendrites per cell. We show that morphology consequences of genetically altered melanocytes can be canceled if cells interact with substrates microstructured by stripes that apply mechanophysical signals in the form of physical topography. The strength of the mechanophysical signal was varied systematically by increasing the height of the microstuctures. Melanocytes respond to surface topographical features that are larger than 50 nm and have lateral confinements smaller than 4 mum. The response of normal and NF1-melanocytes to different topographies was analyzed quantitatively by determining density distributions for the number of dendrites per cell, the angles between dendrites, and the orientation imprinted in the substrate. The synthesis of melanin, a pigment produced by melanocytes, differs in the case of genetically altered NF1 and normal melanocytes. In both cases, the interaction with microstripes enhanced melanin production significantly. This enhanced melanin production is speculated to be caused by the mechanical stabilization of the dendrites by substrate guidance.
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页码:85 / 92
页数:8
相关论文
共 28 条
  • [1] Alberts B., 1994, MOL BIOL CELL
  • [3] The effects of the surface topography of micromachined titanium substrata on cell behavior in vitro and in vivo
    Brunette, DM
    Chehroudi, B
    [J]. JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, 1999, 121 (01): : 49 - 57
  • [4] Geometric control of cell life and death
    Chen, CS
    Mrksich, M
    Huang, S
    Whitesides, GM
    Ingber, DE
    [J]. SCIENCE, 1997, 276 (5317) : 1425 - 1428
  • [5] CHOU LS, 1995, J CELL SCI, V108, P1563
  • [6] Topographical control of cells
    Curtis, A
    Wilkinson, C
    [J]. BIOMATERIALS, 1997, 18 (24) : 1573 - 1583
  • [7] CURTIS AS, 1999, CRIT REV BIOCOMPAT, V5, P343
  • [8] Reactions of cells to topography
    Curtis, ASG
    Wilkinson, CD
    [J]. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 1998, 9 (12) : 1313 - 1329
  • [9] In vitro reaction of endothelial cells to polymer demixed nanotopography
    Dalby, MJ
    Riehle, MO
    Johnstone, H
    Affrossman, S
    Curtis, ASG
    [J]. BIOMATERIALS, 2002, 23 (14) : 2945 - 2954
  • [10] Evidence for the presence of the second allele of the neurofibromatosis type 1 gene in melanocytes derived from cafe au lait macules of NF1 patients
    Eisenbarth, I
    Assum, G
    Kaufmann, D
    Krone, W
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 237 (01) : 138 - 141