in Wiley InterScience (www.interscience.wiley.com).Mechanical forces are important signals in the development and function of the heart and lung, growth of skin and muscle, and maintenance of cartilage and bone. The specific mechanical force ''shear stress'' has been implicated as playing a critical role in the physiological responses of blood vessels through endothelial cell signaling. More recently, studies have shown that shear stress can induce differentiation of stem cells toward both endothelial and bone-producing cell phenotypes. This review will highlight current data supporting the role of shear stress in stem cell fate and will propose potential mechanisms and signaling cascades for transducing shear stress into a biological signal. V

Most cell culture systems grow and spread as contact-inhibited monolayers on flat culture dishes, but the embryonic stem cell (ESC) is one of the cell phenotypes that prefer to self-organize as tightly packed three-dimensional (3D) colonies. ESC also readily form 3D cell aggregates, called embryoid bodies (EB) that partially mimic the spatial and temporal processes of the developing embryo. Here, the rationale for ESC aggregatation, rather than "spreading" on gelatin-coated or mouse embryonic fibroblast (MEF)-coated dishes, is examined through the quantification of the expression levels of adhesion molecules on ESC and the calculation of the adhesive forces on ESC. Modeling each ESC as a dodecahedron, the adhesive force for each ESC-ESC binding was found to be 9.1 x 10(5) pN, whereas, the adhesive force for ESC-MEF binding was found to be an order of magnitude smaller at 7.9 x 10(4) pN. We also show that E-cadherin is the dominating molecule in the ESC-ESC adhesion and blocking E-cadherin leads to a significant reduction in colony formation. Here, we mathematically describe the preference for ESC to self-assemble into ESC-ESC aggregates and 3D colonies, rather than to bind and spread on gelatin or MEF-coated dishes, and have shown that these interactions are predominantly due to E-cadherin expression on ESC.

W hat is systems biology? Aspects of the field can be traced to the mid-20th century, but its recent growth was sparked by the integration of theoretical and structural molecular biology to answer new questions arising from high-throughput, data-rich, functional genomics. New collaborations, institutes, and at least one new research university (our own) established at the turn of this century embraced systems biology to transform "largely descriptive" biology practiced along disciplinary lines into "a quantitative, predictive" interdisciplinary endeavor (1). Almost ten years on, what is systems biology now? As students and faculty drawn together from tissue engineering, molecular and cell biology, physiology, ecology, and evolution into a current topics class of the Quantitative and Systems Biology graduate group at UC Merced, we sought to answer this question to define our course and possibly our futures.Systems Biology: Philosophical Foundations, a collection of papers arising from a 2005 symposium convened by the Department of Molecular Cell Physiology, Vrije Universiteit, Amsterdam, and the first book on the philosophy of systems biology, was a natural starting point. The editors' "Introduction" describes systems biology as the combination of sciences from "physics to ecology, mathematics to medicine and linguistics to chemistry" and the field's purview as "functional biology." Yet, they see systems biology as largely cell biology. In their view the field primarily studies processes that occur in extant life forms; they also note the importance of research into minimal life ("the smallest unit of life among autonomous cells") and the origin of life.Surprisingly, given systems biology's supposed broad embrace, the editors explicitly exclude one discipline: evolutionary biology. They explain, quoting Ernst Mayr (2), that functional and evolutionary biology are "two largely separate fields which differ greatly in methods, Fragestellung [types of questions] and basic concepts." That sentiment is echoed in a chapter on methodologies by Hans Westerhoff and Douglas Kell and again in the editors' "Conclusion" ("systems biology is functional and mechanistic rather than evolutionary biology"), which supposedly summarizes findings of all of the chapters. However, seven of the other 11 chapters discuss the evolution of systems, albeit not always at length. These include thoughtful contributions by William Wimsatt on research programs, Alvaro Moreno on the origin of biological organization, and Evelyn Fox Keller on selforganizing systems.This discrepancy seems to result from the editors'position that functional systems biologists "may use reasoning derived from evolutionary biology" but ignore the evolution of systems. That claim is at best whimsical, and the editors themselves cite homology of DNA sequences as evidence of the "unity of biochemistry," praise "the successes of … phylogenetics," and foresee synergy with "evo-devo." A more convincing exclusion of evolutionary biology could have been damaging. The mantra that...