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Featured researches published by Giovanni Meacci.


Proceedings of the National Academy of Sciences of the United States of America | 2012

Cells test substrate rigidity by local contractions on submicrometer pillars

Saba Ghassemi; Giovanni Meacci; Shuaimin Liu; Alexander Gondarenko; Anurag Mathur; Pere Roca-Cusachs; Michael P. Sheetz; James Hone

Cell growth and differentiation are critically dependent upon matrix rigidity, yet many aspects of the cellular rigidity-sensing mechanism are not understood. Here, we analyze matrix forces after initial cell–matrix contact, when early rigidity-sensing events occur, using a series of elastomeric pillar arrays with dimensions extending to the submicron scale (2, 1, and 0.5 μm in diameter covering a range of stiffnesses). We observe that the cellular response is fundamentally different on micron-scale and submicron pillars. On 2-μm diameter pillars, adhesions form at the pillar periphery, forces are directed toward the center of the cell, and a constant maximum force is applied independent of stiffness. On 0.5-μm diameter pillars, adhesions form on the pillar tops, and local contractions between neighboring pillars are observed with a maximum displacement of ∼60 nm, independent of stiffness. Because mutants in rigidity sensing show no detectable displacement on 0.5-μm diameter pillars, there is a correlation between local contractions to 60 nm and rigidity sensing. Localization of myosin between submicron pillars demonstrates that submicron scale myosin filaments can cause these local contractions. Finally, submicron pillars can capture many details of cellular force generation that are missed on larger pillars and more closely mimic continuous surfaces.


Physical Biology | 2006

Mobility of Min-proteins in Escherichia coli measured by fluorescence correlation spectroscopy

Giovanni Meacci; Jonas Ries; Elisabeth Fischer-Friedrich; Nicoletta Kahya; Petra Schwille; Karsten Kruse

In the bacterium Escherichia coli, selection of the division site involves pole-to-pole oscillations of the proteins MinD and MinE. Different oscillation mechanisms based on cooperative effects between Min-proteins and on the exchange of Min-proteins between the cytoplasm and the cytoplasmic membrane have been proposed. The parameters characterizing the dynamics of the Min-proteins in vivo are not known. It has therefore been difficult to compare the models quantitatively with experiments. Here, we present in vivo measurements of the mobility of MinD and MinE using fluorescence correlation spectroscopy. Two distinct timescales are clearly visible in the correlation curves. While the faster timescale can be attributed to cytoplasmic diffusion, the slower timescale could result from diffusion of membrane-bound proteins or from protein exchange between the cytoplasm and the membrane. We determine the diffusion constant of cytoplasmic MinD to be approximately 16 microm(2) s(-1), while for MinE we find about 10 microm(2) s(-1), independently of the processes responsible for the slower time-scale. The implications of the measured values for the oscillation mechanism are discussed.


Physical Biology | 2005

Min-oscillations in Escherichia coli induced by interactions of membrane-bound proteins

Giovanni Meacci; Karsten Kruse

During division it is of primary importance for a cell to correctly determine the site of cleavage. The bacterium Escherichia coli divides in the center, producing two daughter cells of equal size. Selection of the center as the correct division site is in part achieved by the Min-proteins. They oscillate between the two cell poles and thereby prevent division at these locations. Here, a phenomenological description of these oscillations is presented, where lateral interactions between proteins on the cell membrane play a key role. Solutions to the dynamic equations are compared to experimental findings. In particular, the temporal period of the oscillations is measured as a function of the cell length and found to be compatible with the theoretical prediction.


Proceedings of the National Academy of Sciences of the United States of America | 2010

Intra- and intercellular fluctuations in Min-protein dynamics decrease with cell length

Elisabeth Fischer-Friedrich; Giovanni Meacci; Joe Lutkenhaus; Hugues Chaté; Karsten Kruse

Self-organization of proteins in space and time is of crucial importance for the functioning of cellular processes. Often, this organization takes place in the presence of strong random fluctuations due to the small number of molecules involved. We report on stochastic switching of the Min-protein distributions between the two cell halves in short Escherichia coli cells. A computational model provides strong evidence that the macroscopic switching is rooted in microscopic noise on the molecular scale. In longer bacteria, the switching turns into regular oscillations that are required for positioning of the division plane. As the pattern becomes more regular, cell-to-cell variability also lessens, indicating cell length-dependent regulation of Min-protein activity.


Molecular Biology of the Cell | 2016

α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions

Giovanni Meacci; Haguy Wolfenson; Shuaimin Liu; Matthew R. Stachowiak; Thomas Iskratsch; Anurag Mathur; Saba Ghassemi; Nils C. Gauthier; Erdem Tabdanov; James Lohner; Alexander Gondarenko; Ashok C. Chander; Pere Roca-Cusachs; Ben O’Shaughnessy; James Hone; Michael P. Sheetz

During cell migration, the cell edge undergoes periodic protrusion–retraction cycles. Quantitative analyses of the forces at the cell edge that drive these cycles are provided. We show that α-actinin links local contractile units and the global actin flow forces at the cell edge and present a novel model based on these results.


Proceedings of the National Academy of Sciences of the United States of America | 2009

Dynamics of the bacterial flagellar motor with multiple stators

Giovanni Meacci; Yuhai Tu

The bacterial flagellar motor drives the rotation of flagellar filaments and enables many species of bacteria to swim. Torque is generated by interaction of stator units, anchored to the peptidoglycan cell wall, with the rotor. Recent experiments [Yuan J, Berg HC (2008) Proc Natl Acad Sci USA 105:1182–1185] show that at near-zero load the speed of the motor is independent of the number of stators. Here, we introduce a mathematical model of the motor dynamics that explains this behavior based on a general assumption that the stepping rate of a stator depends on the torque exerted by the stator on the rotor. We find that the motor dynamics can be characterized by two timescales: the moving-time interval for the mechanical rotation of the rotor and the waiting-time interval determined by the chemical transitions of the stators. We show that these two timescales depend differently on the load, and that their cross-over provides the microscopic explanation for the existence of two regimes in the torque-speed curves observed experimentally. We also analyze the speed fluctuation for a single motor by using our model. We show that the motion is smoothed by having more stator units. However, the mechanism for such fluctuation reduction is different depending on the load. We predict that the speed fluctuation is determined by the number of steps per revolution only at low load and is controlled by external noise for high load. Our model can be generalized to study other molecular motor systems with multiple power-generating units.


Nature Cell Biology | 2016

Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices

Haguy Wolfenson; Giovanni Meacci; Shuaimin Liu; Matthew R. Stachowiak; Thomas Iskratsch; Saba Ghassemi; Pere Roca-Cusachs; Ben O’Shaughnessy; James Hone; Michael P. Sheetz


Biophysical Journal | 2013

Sarcomere-Like Units Contract Cell Edges

Giovanni Meacci; Matthew R. Stachowiak; Shuaimin Liu; Thomas Iskratsch; Anurag Mathur; Haguy Wolfenson; Saba Ghassemi; Pere Roca-Cusachs; Erdem Tabdanov; Nils C. Gauthier; Alexander Gondarenko; Ben O'Shaughnessy; James Hone; Michael P. Sheetz


Biophysical Journal | 2014

Lateral Waves during Protrusion-Retraction Cycles of Migrating Cells are Propagating Cracks

Sathish Thiyagarajan; Matthew R. Stachowiak; Giovanni Meacci; Michael P. Sheetz; Ben O'Shaughnessy


Biophysical Journal | 2014

Contractile Forces During ECM Rigidity Sensing are Regulated by Tropomyosin-1

Haguy Wolfenson; Shuaimin Liu; Saba Ghassemi; Giovanni Meacci; James Hone; Michael P. Sheetz

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