Progress Towards Computational 3-D Multicellular Systems Biology

  • Paul Macklin
  • Hermann B. Frieboes
  • Jessica L. Sparks
  • Ahmadreza Ghaffarizadeh
  • Samuel H. Friedman
  • Edwin F. Juarez
  • Edmond Jonckheere
  • Shannon M. Mumenthaler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 936)


Tumors cannot be understood in isolation from their microenvironment. Tumor and stromal cells change phenotype based upon biochemical and biophysical inputs from their surroundings, even as they interact with and remodel the microenvironment. Cancer should be investigated as an adaptive, multicellular system in a dynamical microenvironment. Computational modeling offers the potential to detangle this complex system, but the modeling platform must ideally account for tumor heterogeneity, substrate and signaling factor biotransport, cell and tissue biophysics, tissue and vascular remodeling, microvascular and interstitial flow, and links between all these sub-systems. Such a platform should leverage high-throughput experimental data, while using open data standards for reproducibility. In this chapter, we review advances by our groups in these key areas, particularly in advanced models of tissue mechanics and interstitial flow, open source simulation software, high-throughput phenotypic screening, and multicellular data standards. In the future, we expect a transformation of computational cancer biology from individual groups modeling isolated parts of cancer, to coalitions of groups combining compatible tools to simulate the 3-D multicellular systems biology of cancer tissues.


Multicellular systems biology Computational modeling Tissue engineering  Cancer microenvironment  



This research was supported by University of Southern California (USC) Center for Applied Molecular Medicine (CAMM), the Breast Cancer Research Foundation, the NIH (5U54CA143907, 1R01CA180149), and the USC James H. Zumberge Research and Innovation Fund. We thank Nathan Choi for his 3-D hanging spheroid work in Fig. 12.1.

We thank Alexander Anderson (Moffitt Cancer Center), Mark Chaplain (University of St. Andrews), Vittorio Cristini (University of Texas Health Science Center-Houston), Jasmine Foo (University of Minnesota-Twin Cities), John Lowengrub (University of California-Irvine), Steve McDougall (Heriot-Watt University), Greg Reese (Miami University), Shay Soker (Wake Forest University), and Steven Wise (University of Tennessee-Knoxville), for past and present collaborations. This work would not be where it is today without such valuable collaborations.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Paul Macklin
    • 1
  • Hermann B. Frieboes
    • 2
  • Jessica L. Sparks
    • 3
  • Ahmadreza Ghaffarizadeh
    • 1
  • Samuel H. Friedman
    • 1
  • Edwin F. Juarez
    • 1
    • 4
  • Edmond Jonckheere
    • 4
  • Shannon M. Mumenthaler
    • 1
  1. 1.Lawrence J. Ellison Institute for Transformative MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of BioengineeringUniversity of LouisvilleLouisvilleUSA
  3. 3.Department of Chemical, Paper, and Biomedical EngineeringMiami UniversityOxfordUSA
  4. 4.Department of Electrical EngineeringUniversity of Southern CaliforniaLos AngelesUSA

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