Journal ArticleDOI
The nanomechanical signature of breast cancer
Marija Plodinec,Marko Loparic,Christophe A. Monnier,Ellen C. Obermann,Rosanna Zanetti-Dällenbach,Philipp Oertle,Janne T. Hyotyla,Ueli Aebi,Mohamed Bentires-Alj,Roderick Y. H. Lim,Cora-Ann Schoenenberger +10 more
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TLDR
It is shown using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles, and evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells.Abstract:
Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.read more
Citations
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Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration
Irene Acerbi,Luke Cassereau,Ivory Dean,Quanming Shi,Alfred Au,Catherine C. Park,Yunn-Yi Chen,Jan Liphardt,E. S. Hwang,Valerie M. Weaver +9 more
TL;DR: Findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.
Journal ArticleDOI
Imaging modes of atomic force microscopy for application in molecular and cell biology
Yves F. Dufrêne,Toshio Ando,Ricardo Garcia,David Alsteens,David Martinez-Martin,Andreas Engel,Christoph Gerber,Daniel J. Müller +7 more
TL;DR: The basic principles, advantages and limitations of the most common AFM bioimaging modes are reviewed, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging.
Journal ArticleDOI
Modes of cancer cell invasion and the role of the microenvironment
TL;DR: Future studies will clarify how the combination of stromal network structure, tumor cell signaling and extracellular signaling cues influence cancer cell migration and metastasis.
Journal ArticleDOI
Probing the Stochastic, Motor-Driven Properties of the Cytoplasm Using Force Spectrum Microscopy
Ming Guo,Allen J. Ehrlicher,Allen J. Ehrlicher,Mikkel H. Jensen,Mikkel H. Jensen,Malte Renz,Jeffrey R. Moore,Robert D. Goldman,Jennifer Lippincott-Schwartz,Fred C. MacKintosh,David A. Weitz +10 more
TL;DR: This work introduces force-spectrum-microscopy (FSM) to directly quantify random forces within the cytoplasm of cells and thereby probe stochastic motor activity, and shows that force fluctuations substantially enhance intracellular movement of small and large components.
Journal ArticleDOI
Atomic force microscopy-based mechanobiology
Michael Krieg,Gotthold Fläschner,David Alsteens,Benjamin M. Gaub,Wouter H. Roos,Gijs J.L. Wuite,Hermann E. Gaub,Christoph Gerber,Yves F. Dufrêne,Daniel J. Müller +9 more
TL;DR: The potential of combining AFM with complementary techniques, including optical microscopy and spectroscopy of mechanosensitive fluorescent constructs, super-resolution microscopy, the patch clamp technique and the use of microstructured and fluidic devices to characterize the 3D distribution of mechanical responses within biological systems and to track their morphology and functional state as discussed by the authors.
References
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Journal ArticleDOI
An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments
Warren C. Oliver,George M. Pharr +1 more
TL;DR: In this paper, the authors used a Berkovich indenter to determine hardness and elastic modulus from indentation load-displacement data, and showed that the curve of the curve is not linear, even in the initial stages of the unloading process.
Journal ArticleDOI
New functions for the matrix metalloproteinases in cancer progression
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Journal ArticleDOI
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Matthew J. Paszek,Nastaran Zahir,Kandice R. Johnson,Johnathon N. Lakins,Gabriela I. Rozenberg,Amit Gefen,Cynthia A. Reinhart-King,Susan S. Margulies,Micah Dembo,David Boettiger,Daniel A. Hammer,Valerie M. Weaver +11 more
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Journal ArticleDOI
Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Kandice R. Levental,Hongmei Yu,Laura Kass,Johnathon N. Lakins,Mikala Egeblad,Janine T. Erler,Sheri F. T. Fong,Katalin Csiszar,Amato J. Giaccia,Wolfgang Weninger,Mitsuo Yamauchi,David L. Gasser,Valerie M. Weaver +12 more
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Journal ArticleDOI
Nanomechanical analysis of cells from cancer patients
TL;DR: This work reports the stiffness of live metastatic cancer cells taken from the body fluids of patients with suspected lung, breast and pancreas cancer, and shows that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.