The primary goal of the Jones Lab research group is to determine how the extracellular matrix (ECM), a cell-derived woven and globular protein network that envelopes or contacts most cells within the body—an architectural textile of sorts—changes throughout development and disease, and how alterations in this 3D ECM environment feed back to control cell and tissue behavior at the level of the genome and beyond in real time.
Towards these goals, and in the context of the Sabin+Jones LabStudio collaboration, we began by studying the influence of different extracellular matrix components, such as laminin and type I collagen, on a number of nonlinear biological processes, including tumor formation, cell motility and networking behavior.
Ultimately, at the patho-physiological level, a major aim of our collaborative research is to derive new structural and functional information from each of these dynamic systems in an effort to diagnose, prognosticate and treat human disease.
Over the past three decades, it has been firmly established that 3D cell and tissue architecture, at the level of the ECM, exerts a dominant influence over the genetic makeup of a cell or individual. In this sense, the ECM represents a key phenotypic determinant of cells within tissues. In essence, much of the secret of life resides outside the cell within the extracellular matrix. Importantly, the ECM not only acts as a physical entity, which lends flexibility and physical support to cells within tissues, but it also behaves as an informational entity, an ongoing and historical document that records what transpires in and around a cell during the lifetime of an organism.
Clearly, these biological models are underscored at the cellular and molecular levels by complex non-linear responses to complex and dynamic scenarios. Thus, we posit that a rigorous understanding and analysis of these types of models will allow architects to retool and revaluate how we may negotiate topics such as nonlinear fabrication, feedback and performance in architecture. On the architectural side, rather than seeking direct translation of the science to architecture and vice versa, this research collaboration is about working through biological design problems that give rise to new modes of thinking and working in design and biomedicine.
On the design-studio side, our aim is to introduce biologists to digital and algorithmic architectural tools that may be used to reveal new complexities within the biological systems being studied. Additionally, by specifically examining dynamic cellular systems, our intent is to discover new ways of understanding, revealing and abstracting how these biological systems negotiate issues of auto- and artificial-fabrication. Here structure and material are inextricably linked. Cells and tissues not only produce their own underlying, self-produced fabric, but they modify and respond to this woven, felted or embellished environment. A digital code begets a physical code that informs the physical code and so on.
When cultured on a non-compliant, i.e. hard, 2-D, chemically inert surface, mammary epithelial cells-that become transformed in breast cancer- fail to achieve a normal form, even though they possess the appropriate genes that should enable them to do this. They form flat monolayers that resemble many other cell types.
When cultivated within a compliant, 3-D extracellular matrix within a tissue culture dish, however, cells can be induced to undergo a normal morphogenetic process that resembles the breast in vivo. Once they have achieved this state, the breast epithelium will remain quiescent. However, with cancer, the integrity and quality of the external surface changes, resulting in an inappropriate growth response (deep within the structure) to this modified surface matrix environment.
Understanding precisely how this occurs is a critical step in comprehending this disease, since it is now appreciated that changes in the normal surface architecture of breast epithelial tissue-at the level of the ECM can directly initiate and propagate tumor formation.
This is a profound discovery, since it suggests that by reversing altered cell-ECM interactions, breast cancer cells can be tricked into normal modes of behavior.
In the Surface Design projects, we seek to quantify and spatialize cellular and tissue contour information using normal human mammary epithelial cells cultivated within a 3-D normal or tumor-like microenvironment. Specifically, these projects examine morphogenesis, lumen formation and packing behavior as a response to alterations in tissue surface design. Here, the algorithmic and digital exploration of relationships between interacting cells and their immediate tissue environment gives rise to an abstract, yet deeper understanding of architectural form as it relates to a dynamic boundary condition. In turn, this information has provided new clues as to how the tissue microenvironment may impact cell behavior in breast cancer.