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1.
Orthod Craniofac Res ; 24 Suppl 1: 31-38, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33652500

RESUMO

INTRODUCTION: The purpose of this study was to evaluate the long-term position of erupted third molars after maxillary total arch distalization using modified C-palatal plates (MCPPs) in adolescents and to identify factors associated with these positions. SETTING AND SAMPLE POPULATION: Sixty-two third molars (male: 20, female: 42) in Class II patients treated with MCPPs and thirty-nine teeth for the Control group (male: 22, female: 17). MATERIALS AND METHODS: Samples were analyzed using panoramic radiographs taken initially (T0), after treatment (T1) and after >3 years retention (T2). Third molars were classified as downward (Group A, N = 31; males: 12, females: 19) and upward (Group B, N = 31; males: 8, females: 23) based on their vertical position after treatment. Analysis of variance and multiple logistic regression analysis were performed. RESULTS: The vertical position of the third molars of Group A, Group B, and the Control showed a 2.2, 3.5 and 2.7 mm downward movement at T2. However, there was no difference in the amount of third molar eruption among the groups. Regarding factors affecting the vertical distance of the third molar, Age, C8-OP, ∠8-OP and D7-T at the initial affected vertical position of the third molars after molar distalization (P < .05). CONCLUSIONS: Group A and B showed no difference in the third molar eruption during retention after total arch distalization. This study suggests that it might be unnecessary to extract the developing third molar before molar distalization in Class II adolescents.


Assuntos
Má Oclusão de Angle Classe II , Dente Serotino , Adolescente , Cefalometria , Feminino , Humanos , Masculino , Maxila/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Dente Serotino/diagnóstico por imagem , Dente Serotino/cirurgia , Técnicas de Movimentação Dentária
2.
Elife ; 102021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779550

RESUMO

Single-molecule FRET (smFRET) has become a mainstream technique for studying biomolecular structural dynamics. The rapid and wide adoption of smFRET experiments by an ever-increasing number of groups has generated significant progress in sample preparation, measurement procedures, data analysis, algorithms and documentation. Several labs that employ smFRET approaches have joined forces to inform the smFRET community about streamlining how to perform experiments and analyze results for obtaining quantitative information on biomolecular structure and dynamics. The recent efforts include blind tests to assess the accuracy and the precision of smFRET experiments among different labs using various procedures. These multi-lab studies have led to the development of smFRET procedures and documentation, which are important when submitting entries into the archiving system for integrative structure models, PDB-Dev. This position paper describes the current 'state of the art' from different perspectives, points to unresolved methodological issues for quantitative structural studies, provides a set of 'soft recommendations' about which an emerging consensus exists, and lists openly available resources for newcomers and seasoned practitioners. To make further progress, we strongly encourage 'open science' practices.

3.
J Craniofac Surg ; 32(2): 612-615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704993

RESUMO

OBJECTIVES: To evaluate the linear, angular, and volumetric changes of soft tissue after clockwise repositioning of the maxillo-mandibular complex in skeletal class III patients using three-dimensional (3D) stereophotogrammetry and to determine the correlation between changes in the skeletal and soft tissue variables. METHODS: This study included 18 skeletal class III patients who underwent two-jaw surgery; superior impaction and clockwise rotational movement of the maxilla with the rotation center at upper incisors, and setback of the mandible. Lateral cephalograms and 3D photographs taken before and 6 months after surgery were compared. RESULTS: After maxillary impaction of anteriorly 1.7 mm and posteriorly 3.1 mm, and mandibular setback of 8.7 mm, the volume of lower lip and chin region decreased significantly by 33.6 cm3 (13% net change, P < 0.001), while paranasal and upper lip region volume increased by 3.2 cm3 (2%) and 7.2 cm3 (4%), respectively. CONCLUSION: The clockwise rotation of maxillo-mandibular complex in class III patients significantly reduced lower lip and chin volume with minimal increase in paranasal and upper lip volumes. 3D stereophotogrammetry can provide quantitative evaluation of facial soft tissue volumetric changes.

4.
J Craniofac Surg ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33710053

RESUMO

ABSTRACT: The authors analyzed the three-dimensional postoperative condylar position change across the plating systems. This retrospective study was conducted with the patients who underwent bilateral sagittal split ramus osteotomy with setback surgery. The condylar change was analyzed from preoperative cone-beam computed tomography to postoperative 1 month (T1) and postoperative 6 months (T2) using superimposition software, automatically merging based on the anterior cranial base. The condylar changes during T1 and T2 were analyzed across the four types of plates (4-hole sliding, heart-shaped, 3-hole sliding, and 4-hole conventional) Mean intraclass correlation coefficient values were consistently high for each measurement (>0.850). During T1, the conventional plate had a decreased condylar anterior distance when compared with the 3-hole sliding plate (P = 0.032). During T2, the conventional plate had an increased condylar posterior distance when compared with the 3-hole sliding plate (P = 0.031). Superimposition software based on the anterior cranial base could be available for measurement of condylar position with highly reproducible results. After bilateral sagittal split ramus osteotomy, the 3-hole sliding plate could effectively compensate for the anterior displacement of the condyle compared to other plates.

5.
Am J Orthod Dentofacial Orthop ; 159(4): 470-479, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33558030

RESUMO

INTRODUCTION: The aims of this study were to evaluate the long-term skeletodental effects, the volume of maxillary tuberosity, and airway space changes after maxillary molar distalization using modified C-palatal plate (MCPP) in adolescents with Class II malocclusion. METHODS: The sample consisted of 20 adolescent patients (MCPP group; mean age, 12.9 ± 1.0 year) who underwent bilateral distalization of their maxillary dentition and 20 subjects as a control group. In the MCPP group, cone-beam computed tomography images were taken before distalization, at the end of the treatment, and during retention with a minimum of a 3-year posttreatment follow up period. Repeated measures ANOVA followed by post-hoc analysis with the Bonferroni test were used to identify significant differences between time points. RESULTS: After the long-term observation period, sagittal skeletal and dental relationships were maintained (there were no significant changes in ANB, occlusal plane angle, and overjet postretention). The vertical skeletal dimension did not change during treatment and was stable at the long-term follow-up (the mandibular plane angle and ANS-Me were relatively well maintained). The volume of the maxillary tuberosity showed no significant change during long-term retention. However, the volume was significantly smaller in the treatment group than in the control group (P <0.0001). There were no significant airway space changes after distalization and the postretention period. In addition, there was no significant difference between the MCPP and control groups. CONCLUSIONS: Improved sagittal skeletal and dental relationships because of treatment were maintained in the long-term evaluation. There was no negative long-term effect on airway space associated with the maxillary arch distalization. Therefore, these findings might be beneficial for clinicians in diagnosis and treatment planning for Class II malocclusion in adolescents.


Assuntos
Má Oclusão de Angle Classe II , Técnicas de Movimentação Dentária , Adolescente , Cefalometria , Criança , Tomografia Computadorizada de Feixe Cônico , Humanos , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/terapia , Maxila/diagnóstico por imagem , Desenho de Aparelho Ortodôntico
6.
Clin Oral Investig ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475827

RESUMO

OBJECTIVES: The purpose of this retrospective study was to evaluate the accuracy of intraoral scan (IOS) images in the maxillary and mandibular arches with orthodontic brackets. MATERIAL AND METHODS: From digital impressions of 140 patients who underwent orthodontic treatment, consecutive IOS images were selected based on standardized inclusion criteria: Two pre-orthodontic IOS images (IOS1 and IOS2) of permanent dentition with fully erupted second molars and IOS images obtained immediately after orthodontic bracket bonding (IOSb). Superimpositions were performed to evaluate the reproducibility of repeated IOS images. Accuracy of IOSb images was analyzed by comparing the average surface errors between IOS1c and IOS2c images, which were IOS images cut based on the same region of the interest as between IOS1 and IOSb images. RESULTS: A total of 84 IOS images was analyzed. The average surface errors between IOS1 and IOS2 images were 57 ± 8 µm and 59 ± 14 µm in the maxillary and mandibular arch, respectively, and their reliability was almost perfect. The average errors between IOSb and IOS1c images exhibited an increase, which measured 97 ± 28 µm in the maxillary arch and 95 ± 29 µm in the mandibular arch. These surface deviations between IOSb and IOS1c images were significantly larger in each region as well as entire dentition (P < 0.001) compared to those between IOS1c and IOS2c images. CONCLUSIONS: The average surface errors of the scans with brackets showed increased values compared with those without brackets. This suggests that orthodontic brackets could affect the trueness of intraoral scan images. CLINICAL RELEVANCE: It is necessary for clinicians to consider the effect of brackets on digital impression when using IOS images in orthodontic patients.

7.
Angle Orthod ; 91(1): 22-29, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33339047

RESUMO

OBJECTIVES: To compare the dental and skeletal treatment effects after total arch distalization using modified C-palatal plates (MCPPs) on adolescent patients with hypo- and hyperdivergent Class II malocclusion. MATERIALS AND METHODS: The study group included 40 patients with Class II malocclusion (18 boys and 22 girls, mean age = 12.2 ± 1.4 years) treated with MCPPs. Fixed orthodontic treatment started with the distalizing process in both groups. Participants were divided into hypo- or hyperdivergent groups based on their pretreatment Frankfort mandibular plane angle (FMA) ≤22° or ≥28°, respectively. Pre- and posttreatment lateral cephalograms were digitized, and 23 variables were measured and compared for both groups using paired and independent t-tests. RESULTS: The hyper- and hypodivergent groups showed 2.7 mm and 4.3 mm of first molar crown distalizing movement, respectively (P < .001). The hypodivergent group had a slight 2.2° crown distal tipping of first molars compared with 0.3° in the hyperdivergent group. After distalization, the FMA increased 3.1° and 0.3°, in the hypodivergent and hyperdivergent groups, respectively (P < .001). SNA decreased in the hypodivergent group, while other skeletal variables presented no statistically significant differences in the changes between the groups. CONCLUSIONS: The hypodivergent group showed more distal and tipping movement of the maxillary first molar and increased FMA than the hyperdivergent group. Therefore, clinicians must consider vertical facial types when distalizing molars using MCPPs in Class II nonextraction treatment.


Assuntos
Má Oclusão de Angle Classe II , Desenho de Aparelho Ortodôntico , Adolescente , Cefalometria , Feminino , Humanos , Masculino , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/terapia , Maxila , Técnicas de Movimentação Dentária
8.
Angle Orthod ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33289781

RESUMO

OBJECTIVES: To compare the dental and skeletal treatment effects after total arch distalization using modified C-palatal plates (MCPPs) on adolescent patients with hypo- and hyperdivergent Class II malocclusion. MATERIALS AND METHODS: The study group included 40 patients with Class II malocclusion (18 boys and 22 girls, mean age = 12.2 ± 1.4 years) treated with MCPPs. Fixed orthodontic treatment started with the distalizing process in both groups. Participants were divided into hypo- or hyperdivergent groups based on their pretreatment Frankfort mandibular plane angle (FMA) ≤22° or ≥28°, respectively. Pre- and posttreatment lateral cephalograms were digitized, and 23 variables were measured and compared for both groups using paired and independent t-tests. RESULTS: The hyper- and hypodivergent groups showed 2.7 mm and 4.3 mm of first molar crown distalizing movement, respectively (P < .001). The hypodivergent group had a slight 2.2° crown distal tipping of first molars compared with 0.3° in the hyperdivergent group. After distalization, the FMA increased 3.1° and 0.3°, in the hypodivergent and hyperdivergent groups, respectively (P < .001). SNA decreased in the hypodivergent group, while other skeletal variables presented no statistically significant differences in the changes between the groups. CONCLUSIONS: The hypodivergent group showed more distal and tipping movement of the maxillary first molar and increased FMA than the hyperdivergent group. Therefore, clinicians must consider vertical facial types when distalizing molars using MCPPs in Class II nonextraction treatment.

9.
Maxillofac Plast Reconstr Surg ; 42(1): 30, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32884928

RESUMO

Background: Dental studies of precocious puberty have focused on examination of jaw and dentition growth. The aim of the study was to analyze the relationship between precocious puberty and maxillary dental developmental abnormalities (DDAs). Methods: This retrospective study was conducted on the Korean patients in whom dental panoramic and hand-wrist radiographs had been taken before they were 15 years of age. The maxillary DDAs were assessed as mesiodens, congenital missing teeth, peg-shape lateral incisors, or impacted teeth. The chronological ages of the control group members were within the normal range of the hand-wrist bone age. Others with a peak luteinizing hormone of ≥ 5 and < 5 IU/L were allocated to central precocious puberty (CPP) and peripheral precocious puberty (PPP), respectively. Results: Of the enrolled 270 patients, 195, 52, and 23 were allocated to the control, CPP, and PPP groups, respectively. The maxillary DDAs were significantly more prevalent in the CPP group than in the other groups. Among those with maxillary DDA, the mesiodens predominated. Age- and sex-adjusted multivariate analysis revealed maxillary DDA (odds ratio, 3.36; 95% CI, 1.60-7.05) and especially mesiodens (odds ratio, 5.52; CI, 2.29-13.28) to be significantly associated with CPP. Conclusions: Maxillary DDAs were significantly more prevalent in the CPP group than in the PPP or control groups. Among the many types of maxillary DDAs, mesiodens was significantly associated with CPP and may be considered a predictor of the development of CPP.

10.
J World Fed Orthod ; 9(3): 129-136, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32873518

RESUMO

OBJECTIVE: The aim of this study was to compare the facial esthetic standards between Paraguayan and Korean beauty pageant contestants as well as to evaluate the deviation in Farkas proportion indexes (PI) from the golden ratio for each group using three-dimensional (3D) stereophotogrammetric analysis. METHODS: 3D soft tissue images of 34 Miss Paraguay (MP) and 54 Miss Korea (MK) pageant contestants were obtained. The 3D images were digitized and 52 measurements and ratios were calculated. One-way multivariate analysis of variance was applied to compare the two groups. One-sample t-test was applied to assess the differences between the PI of each group and the golden ratio. RESULTS: The MP group showed greater mouth width, total vermilion perimeter, and lower lip protrusion (P < 0.001) than the MK group. Meanwhile, the MK group showed longer forehead height and total facial height (P = 0.002 and P < 0.001, respectively). All Farkas PIs in each group showed significant differences from the golden ratio except for PI19 (upper/lower vermilion heights). CONCLUSIONS: Paraguayans favor rectangular faces with wide mouths and large lips, especially the lower lips, whereas Koreans prefer long tapered faces with small mouths and lips. All proportion indexes were significantly different from the golden ratio except for PI19. Therefore, it would be beneficial for clinicians to consider the differences in ethnic preferences in facial esthetics during diagnosis and treatment planning.

11.
J Craniofac Surg ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32833812

RESUMO

OBJECTIVES: To evaluate the linear, angular, and volumetric changes of soft tissue after clockwise repositioning of the maxillo-mandibular complex in skeletal class III patients using three-dimensional (3D) stereophotogrammetry and to determine the correlation between changes in the skeletal and soft tissue variables. METHODS: This study included 18 skeletal class III patients who underwent two-jaw surgery; superior impaction and clockwise rotational movement of the maxilla with the rotation center at upper incisors, and setback of the mandible. Lateral cephalograms and 3D photographs taken before and 6 months after surgery were compared. RESULTS: After maxillary impaction of anteriorly 1.7 mm and posteriorly 3.1 mm, and mandibular setback of 8.7 mm, the volume of lower lip and chin region decreased significantly by 33.6 cm (13% net change, P < 0.001), while paranasal and upper lip region volume increased by 3.2 cm (2%) and 7.2 cm (4%), respectively. CONCLUSION: The clockwise rotation of maxillo-mandibular complex in class III patients significantly reduced lower lip and chin volume with minimal increase in paranasal and upper lip volumes. 3D stereophotogrammetry can provide quantitative evaluation of facial soft tissue volumetric changes.

13.
Elife ; 92020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32297860

RESUMO

Deinococcus radiodurans (DR) survives in the presence of hundreds of double-stranded DNA (dsDNA) breaks by efficiently repairing such breaks. RecO, a protein that is essential for the extreme radioresistance of DR, is one of the major recombination mediator proteins in the RecA-loading process in the RecFOR pathway. However, how RecO participates in the RecA-loading process is still unclear. In this work, we investigated the function of drRecO using single-molecule techniques. We found that drRecO competes with the ssDNA-binding protein (drSSB) for binding to the freely exposed ssDNA, and efficiently displaces drSSB from ssDNA without consuming ATP. drRecO replaces drSSB and dissociates it completely from ssDNA even though drSSB binds to ssDNA approximately 300 times more strongly than drRecO does. We suggest that drRecO facilitates the loading of RecA onto drSSB-coated ssDNA by utilizing a small drSSB-free space on ssDNA that is generated by the fast diffusion of drSSB on ssDNA.

14.
Korean J Orthod ; 50(2): 120-128, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32257937

RESUMO

Objective: The aims of the present study were to evaluate the changes in the maximum lip-closing force (MLF) after orthodontic treatment with or without premolar extractions and verify the correlation of these changes with dentoskeletal changes. Methods: In total, 17 women who underwent nonextraction orthodontic treatment and 15 women who underwent orthodontic treatment with extraction of all four first premolars were included in this retrospective study. For all patients, lateral cephalograms and dental models were measured before (T0) and after (T1) treatment. In addition, MLF was measured at both time points using the Lip De Cum LDC-110R® device. Statistical analyses were performed to evaluate changes in clinical variables and MLF and their correlations. Results: Both groups showed similar skeletal patterns, although the extraction group showed greater proclination of the maxillary and mandibular incisors and lip protrusion compared to the nonextraction group at T0. MLF at T0 was comparable between the two groups. The reduction in the arch width and depth and incisor retroclination from T0 to T1 were more pronounced in the extraction group than in the nonextraction group. MLF in the extraction group significantly increased during the treatment period, and this increase was significantly greater than that in the nonextraction group. The increase in MLF was found to be correlated with the increase in the interincisal angle and decrease in the intermolar width, arch depth, and incisor-mandibular plane angle. Conclusions: This study suggests that MLF increases to a greater extent during extraction orthodontic treatment than during nonextraction orthodontic treatment.

15.
J Oral Maxillofac Surg ; 77(5): 1072.e1-1072.e9, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30707985

RESUMO

PURPOSE: The aims of this study were to compare the presurgical conditions, surgical changes, and postsurgical changes in patients with skeletal Class III malocclusion with different degrees of horizontal relapse after mandibular setback surgery (MS) with minimal presurgical orthodontics (MPO) and to identify the factors contributing to this relapse. MATERIALS AND METHODS: For this retrospective study, 33 consecutive patients who underwent MS-MPO were selected. Lateral cephalograms were taken preoperatively (T0), 1 month after surgery (T1), and at orthodontic debonding (T2). Patients were divided into low relapse (LR; n = 18; relapse, <1 mm) and high relapse (HR; n = 15; relapse, >2 mm) groups based on the cephalometric distance of mandibular horizontal relapse. Paired t test, independent t test, and Pearson correlation analysis were used to evaluate surgical (T0 to T1) and postsurgical (T1 to T2) changes in the skeletodental variables and to explore the relation between surgical changes and horizontal relapse. RESULTS: Compared with the LR group, the HR group exhibited more upward movement with counterclockwise rotation of the mandible from T1 to T2. The HR group presented at T0 with a more prognathic mandible, greater vertical facial height, and a positive overbite. In addition, the HR group presented more posterior movement with clockwise rotation of the mandible, increased overjet, and decreased overbite from T0 to T1. Horizontal relapse of the mandible was positively correlated with the amount of setback and clockwise rotation of the mandible and the change in overjet and was negatively correlated with the change in overbite. CONCLUSIONS: Mandibular instability was related to the extent of setback and clockwise rotation of the mandible, decreased overbite, and increased overjet during MS-MPO.


Assuntos
Ortodontia , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Seguimentos , Humanos , Má Oclusão de Angle Classe III , Mandíbula/cirurgia , Maxila , Recidiva , Estudos Retrospectivos
16.
PLoS Biol ; 16(12): e2006660, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30543635

RESUMO

Interactions between membrane proteins are poorly understood despite their importance in cell signaling and drug development. Here, we present a co-immunoimmobilization assay (Co-II) enabling the direct observation of membrane protein interactions in single living cells that overcomes the limitations of currently prevalent proximity-based indirect methods. Using Co-II, we investigated the transient homodimerizations of epidermal growth factor receptor (EGFR) and beta-2 adrenergic receptor (ß2-AR) in living cells, revealing the differential regulation of these receptors' dimerizations by molecular conformations and microenvironment in a plasma membrane. Co-II should provide a simple, rapid, and robust platform for visualizing both weak and strong protein interactions in the plasma membrane of living cells.


Assuntos
Imunoprecipitação/métodos , Mapeamento de Interação de Proteínas/métodos , Análise de Célula Única/métodos , Linhagem Celular , Membrana Celular/metabolismo , Receptores ErbB/fisiologia , Humanos , Proteínas de Membrana/fisiologia , Ligação Proteica/fisiologia , Receptores Adrenérgicos beta 2/fisiologia , Transdução de Sinais
18.
Nat Methods ; 15(9): 669-676, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30171252

RESUMO

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods.


Assuntos
Transferência Ressonante de Energia de Fluorescência/métodos , Laboratórios/normas , Reprodutibilidade dos Testes
19.
J Am Chem Soc ; 140(25): 7778-7781, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29874063

RESUMO

Understanding the underlying principles for the target-specific nuclease activity of CRISPR/Cas9 is a prerequisite to minimize its off-target DNA cleavage for genome engineering applications. Here, we show that the noncatalytic REC2 domain of Cas9 nuclease plays a crucial role in off-target discrimination. Using single-molecule fluorescence methods, we investigate conformational dynamics of the non-target strand (NTS) of DNA interacting with Cas9 and find that REC2 regulates the NTS rearrangement for cleavage reaction with the help of positively charged residues on its surface. This mechanistic model for the target specificity of Cas9 provides molecular insights for the rational approach to Cas9 engineering for highly specific genome editing.


Assuntos
Sistemas CRISPR-Cas/genética , DNA/genética
20.
Chem Sci ; 8(7): 4823-4832, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28959404

RESUMO

Cellular processes occur through the orchestration of multi-step molecular reactions. Reaction progress kinetic analysis (RPKA) can provide the mechanistic details to elucidate the multi-step molecular reactions. However, current tools have limited ability to simultaneously monitor dynamic variations in multiple complex states at the single molecule level to apply RPKA in living cells. In this research, a single particle tracking-based reaction progress kinetic analysis (sptRPKA) was developed to simultaneously determine the kinetics of multiple states of protein complexes in the membrane of a single living cell. The subpopulation ratios of different states were quantitatively (and statistically) reliably extracted from the diffusion coefficient distribution rapidly acquired by single particle tracking at constant and high density over a long period of time using super-resolution microscopy. Using sptRPKA, a series of molecular mechanisms of epidermal growth factor receptor (EGFR) cellular processing induced by cetuximab were investigated. By comprehensively measuring the rate constants and cooperativity of the molecular reactions involving four EGFR complex states, a previously unknown intermediate state was identified that represents the rate limiting step responsible for the selectivity of cetuximab-induced EGFR endocytosis to cancer cells.

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